Triazol[4,5-d] pyramidine derivatives and their use as purinergic receptor antagonists

ABSTRACT

The use of a compound of formula (I): 
                         
wherein
     R 1  is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR 5 R 6 , NR 4 COR 5 , NR 4 CONR 5 R 6 , NR 4 CO 2 R 7  and NR 4 SO 2 R 7 ;   R 2  is selected from aryl attached via an unsaturated carbon;   R 3  is selected from H, alkyl, COR 5 , CO 2 R 7 , CONR 5 R 6 , CONR 4 NR 5 R 6  and SO 2 R 7 ;   R 4 , R 5  and R 6  are independently selected from H, alkyl and aryl or where R 5  and R 6  are in an NR 5 R 6  group, R 5  and R 6  may be linked to form a heterocyclic group, or where R 4 , R 5  and R 6  are in a (CONR 4 NR 5 R 6 ) group, R 4  and R 5  may be linked to form a heterocyclic group; and   R 7  is selected from alkyl and aryl,
 
or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A 2A  receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson&#39;s disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional of U.S. patent application Ser. No.11/507,625 filed on Aug. 22, 2006 now U.S. Pat. No. 7,405,219 which is aContinuation of U.S. patent application Ser. No. 10/250,942, filed onOct. 8, 2003, now U.S. Pat. No. 7,141,575 which is the National Phase ofPCT/GB02/00091, filed Jan. 10, 2002, and published as WO 02/055083,which claims priority to Great Britain Application No. 0100624.6, filedJan. 10, 2001, the contents of all are hereby incorporated by reference.

The present invention relates to triazolo[4,5-d]pyrimidine derivativesand their use in therapy. In particular, the present invention relatesto the treatment of disorders in which the reduction of purinergicneurotransmission could be beneficial. The invention relates inparticular to the blockade of adenosine receptors and particularlyadenosine A_(2A) receptors, and to the treatment of movement disorderssuch as Parkinson's disease.

Movement disorders constitute a serious health problem, especiallyamongst the elderly sector of the population. These movement disordersare often the result of brain lesions. Disorders involving the basalganglia which result in movement disorders include Parkinson's disease,Huntington's chorea and Wilson's disease. Furthermore, dyskinesias oftenarise as sequelae of cerebral ischaemia and other neurologicaldisorders.

There are four classic symptoms of Parkinson's disease: tremor,rigidity, akinesia and postural changes. The disease is also commonlyassociated with depression, dementia and overall cognitive decline.Parkinson's disease has a prevalence of 1 per 1,000 of the totalpopulation. The incidence increases to 1 per 100 for those aged over 60years. Degeneration of dopaminergic neurones in the substantia nigra andthe subsequent reductions in interstitial concentrations of dopamine inthe striatum are critical to the development of Parkinson's disease.Some 80% of cells from the substantia nigra need to be destroyed beforethe clinical symptoms of Parkinson's disease are manifested.

Current strategies for the treatment of Parkinson's disease are based ontransmitter replacement therapy (L-dihydroxyphenylacetic acid (L-DOPA)),inhibition of monoamine oxidase (e.g. Deprenyl®), dopamine receptoragonists (e.g. bromocriptine and apomorphine) and anticholinergics (e.g.benztrophine, orphenadrine). Transmitter replacement therapy inparticular does not provide consistent clinical benefit, especiallyafter prolonged treatment when “on-off” symptoms develop, and thistreatment has also been associated with involuntary movements ofathetosis and chorea, nausea and vomiting. Additionally currenttherapies do not treat the underlying neurodegenerative disorderresulting in a continuing cognitive decline in patients. Despite newdrug approvals, there is still a medical need in terms of improvedtherapies for movement disorders, especially Parkinson's disease. Inparticular, effective treatments requiring less frequent dosing,effective treatments which are associated with less severe side-effects,and effective treatments which control or reverse the underlyingneurodegenerative disorder, are required.

Blockade of A₂ adenosine receptors has recently been implicated in thetreatment of movement disorders such as Parkinson's disease (Richardson,P. J. et al., Trends Pharmacol. Sci. 1997, 18, 338-344) and in thetreatment of cerebral ischaemia (Gao, Y. and Phillis, J. W., Life Sci.1994, 55, 61-65). The potential utility of adenosine A_(2A) receptorantagonists in the treatment of movement disorders such as Parkinson'sDisease has recently been reviewed (Mally, J. and Stone, T. W., CNSDrugs, 1998, 10, 311-320).

Adenosine is a naturally occurring purine nucleoside which has a widevariety of well-documented regulatory functions and physiologicaleffects. The central nervous system (CNS) effects of this endogenousnucleoside have attracted particular attention in drug discovery, owingto the therapeutic potential of purinergic agents in CNS disorders(Jacobson, K. A. et al., J. Med. Chem. 1992, 35, 407-422). Thistherapeutic potential has resulted in considerable recent researchendeavour within the field of adenosine receptor agonists andantagonists (Bhagwhat, S. S.; Williams, M. Exp. Opin. Ther. Patents1995, 5,547-558).

Adenosine receptors represent a subclass (P₁) of the group of purinenucleotide and nucleoside receptors known as purinoreceptors. The mainpharmacologically distinct adenosine receptor subtypes are known as A₁,A_(2A), A_(2B) (of high and low affinity) and A₃ (Fredholm, B. B., etal., Pharmacol. Rev. 1994, 46, 143-156). The adenosine receptors arepresent in the CNS (Fredholm, B. B., News Physiol. Sci., 1995, 10,122-128).

The design of P₁ receptor-mediated agents has been reviewed (Jacobson,K. A., Suzuki, F., Drug Dev. Res., 1997, 39, 289-300; Baraldi, P. G. etal., Curr. Med. Chem. 1995, 2, 707-722), and such compounds are claimedto be useful in the treatment of cerebral ischemia or neurodegenerativedisorders, such as Parkinson's disease (Williams, M. and Burnstock, G.Purinergic Approaches Exp. Ther. (1997), 3-26. Editor: Jacobson, KennethA.; Jarvis, Michael F. Publisher: Wiley-Liss, New York, N.Y.)

It has been speculated that xanthine derivatives such as caffeine mayoffer a form of treatment for attention-deficit hyperactivity disorder(ADHD). A number of studies have demonstrated a beneficial effect ofcaffeine on controlling the symptoms of ADHD (Garfinkel, B. D. et al.,Psychiatry, 1981, 26, 395-401). Antagonism of adenosine receptors isthought to account for the majority of the behavioural effects ofcaffeine in humans and thus blockade of adenosine A_(2A) receptors mayaccount for the observed effects of caffeine in ADHD patients. Thereforea selective A_(2A) receptor antagonist may provide an effectivetreatment for ADHD but without the unwanted side-effects associated withcurrent therapy.

Adenosine receptors have been recognised to play an important role inregulation of sleep patterns, and indeed adenosine antagonists such ascaffeine exert potent stimulant effects and can be used to prolongwakefulness (Porkka-Heiskanen, T. et al., Science, 1997, 276,1265-1268). Recent evidence suggests that a substantial part of theactions of adenosine in regulating sleep is mediated through theadenosine A_(2A) receptor (Satoh, S., et al., Proc. Natl. Acad. Sci.,USA, 1996). Thus, a selective A_(2A) receptor antagonist may be ofbenefit in counteracting excessive sleepiness in sleep disorders such ashypersomnia or narcolepsy.

It has recently been observed that patients with major depressiondemonstrate a blunted response to adenosine agonist-induced stimulationin platelets, suggesting that a dysregulation of A_(2A) receptorfunction may occur during depression (Berk, M. et al, 2001, Eur.Neuropsychopharmacol. 11, 183-186). Experimental evidence in animalmodels has shown that blockade of A_(2A) receptor function confersantidepressant activity (El Yacoubi, M et al. Br. J. Pharmacol. 2001,134, 68-77). Thus, A_(2A) receptor antagonists may offer a novel therapyfor the treatment of major depression and other affective disorders inpatients.

The pharmacology of adenosine A_(2A) receptors has been reviewed(Ongini, E.; Fredholm, B. B. Trends Pharmacol. Sci. 1996, 17(10),364-372). One potential underlying mechanism in the aforementionedtreatment of movement disorders by the blockade of A₂ adenosinereceptors is the evidence of a functional link between adenosine A_(2A)receptors to dopamine D₂ receptors in the CNS. Some of the early studies(e.g. Ferre, S. et al., Stimulation of high-affinity adenosine A₂receptors decreases the affinity of dopamine D₂ receptors in ratstriatal membranes. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7238-41)have been summarised in two more recent articles (Fuxe, K. et al.,Adenosine Adenine Nucleotides Mol. Biol. Integr. Physiol., [Proc. Int.Symp.], 5th (1995), 499-507. Editors: Belardinelli, Luiz; Pelleg, Amir.Publisher: Kluwer, Boston, Mass.; Ferre, S. et al., Trends Neurosci.1997, 20, 482-487).

As a result of these investigations into the functional role ofadenosine A_(2A) receptors in the CNS, especially in vivo studieslinking A₂ receptors with catalepsy (Ferre et al., Neurosci. Lett. 1991,130, 162-4; Mandhane, S. N. et al., Eur. J. Pharmacol. 1997, 328,135-141) investigations have been made into agents which selectivelybind to adenosine A_(2A) receptors as potentially effective treatmentsfor Parkinson's disease.

While many of the potential drugs for treatment of Parkinson's diseasehave shown benefit in the treatment of movement disorders, an advantageof adenosine A_(2A) antagonist therapy is that the underlyingneurodegenerative disorder may also be treated. The neuroprotectiveeffect of adenosine A_(2A) antagonists has been reviewed (Ongini, E.;Adami, M.; Ferri, C.; Bertorelli, R., Ann. N.Y. Acad. Sci. 1997, 825(Neuroprotective Agents), 30-48). In particular, compelling recentevidence suggests that blockade of A_(2A) receptor function confersneuroprotection against MPTP-induced neurotoxicity in mice (Chen, J-F.,J. Neurosci. 2001, 21, RC143). In addition, several recent studies haveshown that consumption of dietary caffeine, a known adenosine A_(2A)receptor antagonist, is associated with a reduced risk of Parkinson'sdisease in man (Ascherio, A. et al, Ann Neurol., 2001, 50, 56-63; Ross GW, et al., JAMA, 2000, 283, 2674-9). Thus, A_(2A) receptor antagonistsmay offer a novel treatment for conferring neuroprotection inneurodegenerative diseases such as Parkinson's disease.

Xanthine derivatives have been disclosed as adenosine A₂ receptorantagonists as useful for treating various diseases caused byhyperfunctioning of adenosine A₂ receptors, such as Parkinson's disease(see, for example, EP-A-565377).

One prominent xanthine-derived adenosine A_(2A) selective antagonist isCSC [8-(3-chlorostyryl)caffeine] (Jacobson et al., FEBS Lett., 1993,323, 141-144).

Theophylline (1,3-dimethylxanthine), a bronchodilator drug which is amixed antagonist at adenosine A₁ and A_(2A) receptors, has been studiedclinically. To determine whether a formulation of this adenosinereceptor antagonist would be of value in Parkinson's disease an opentrial was conducted on 15 Parkinsonian patients, treated for up to 12weeks with a slow release oral theophylline preparation (150 mg/day),yielding serum theophylline levels of 4.44 mg/L after one week. Thepatients exhibited significant improvements in mean objective disabilityscores and 11 reported moderate or marked subjective improvement (Mally,J., Stone, T. W. J. Pharm. Pharmacol. 1994, 46, 515-517).

KF 17837 [(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine] isa selective adenosine A_(2A) receptor antagonist which on oraladministration significantly ameliorated the cataleptic responsesinduced by intracerebroventricular administration of an adenosine A_(2A)receptor agonist, CGS 21680. KF 17837 also reduced the catalepsy inducedby haloperidol and reserpine. Moreover, KF 17837 potentiated theanticataleptic effects of a subthreshold dose of L-DOPA plusbenserazide, suggesting that KF 17837 is a centrally active adenosineA_(2A) receptor antagonist and that the dopaminergic function of thenigrostriatal pathway is potentiated by adenosine A_(2A) receptorantagonists (Kanda, T. et al., Eur. J. Pharmacol. 1994, 256, 263-268).The structure activity relationship (SAR) of KF 17837 has been published(Shimada, J. et al., Bioorg. Med. Chem. Lett. 1997, 7, 2349-2352).Recent data has also been provided on the A_(2A) receptor antagonistKW-6002 (Kuwana, Y et al., Soc. Neurosci. Abstr. 1997, 23, 119.14; andKanda, T. et al., Ann. Neurol. 1998, 43(4), 507-513).

New non-xanthine structures sharing these pharmacological propertiesinclude SCH 58261 and its derivatives (Baraldi, P. G. et al.,Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives: Potent andSelective A_(2A) Adenosine Antagonists. J. Med. Chem. 1996, 39,1164-71). SCH 58261(7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine)is reported as effective in the treatment of movement disorders (Ongini,E. Drug Dev. Res. 1997, 42(2), 63-70) and has been followed up by alater series of compounds (Baraldi, P. G. et al., J. Med. Chem. 1998,41(12), 2126-2133).

The foregoing discussion indicates that a potentially effectivetreatment for movement disorders in humans would comprise agents whichact as antagonists at adenosine A_(2A) receptors.

It has now been found that triazolo[4,5-d]pyrimidine derivatives, whichare structurally unrelated to known adenosine receptor antagonists,exhibit unexpected antagonist binding affinity at adenosine (P₁)receptors, and in particular at the adenosine A_(2A) receptor. Suchcompounds may therefore be useful for the treatment of disorders inwhich the blocking of purine receptors, particularly adenosine receptorsand more particularly adenosine A_(2A) receptors, may be beneficial. Inparticular such compounds may be suitable for the treatment of movementdisorders, such as disorders of the basal ganglia which result indyskinesias. Disorders of particular interest include Parkinson'sdisease, Alzheimer's disease, spasticity, Huntington's chorea andWilson's disease.

Such compounds may also be particularly suitable for the treatment ofdepression, cognitive or memory impairment including Alzheimer'sdisease, acute or chronic pain, ADHD and narcolepsy, or forneuroprotection.

According to the present invention there is provided the use of acompound of formula (I):

wherein

-   R₁ is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio,    arylthio, halogen, CN, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and    NR₄SO₂R₇;-   R₂ is selected from aryl attached via an unsaturated carbon;-   R₃ is selected from H, alkyl, COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆ and    SO₂R₇;-   R₄, R₅ and R₆ are independently selected from H, alkyl and aryl or    where R₅ and R₆ are in an NR₅R₆ group, R₅ and R₆ may be linked to    form a heterocyclic group, or where R₄, R₅ and R₆ are in a    (CONR₄NR₅R₆) group, R₄ and R₅ may be linked to form a heterocyclic    group; and-   R₇ is selected from alkyl and aryl,    or a pharmaceutically acceptable salt thereof or prodrug thereof, in    the manufacture of a medicament for the treatment or prevention of a    disorder in which the blocking of purine receptors, particularly    adenosine receptors and more particularly A_(2A) receptors, may be    beneficial.

As used herein, the term “alkyl” means a branched or unbranched, cyclicor acyclic, saturated or unsaturated (e.g. alkenyl oralkynyl)hydrocarbyl radical which may be substituted or unsubstituted.Where cyclic, the alkyl group is preferably C₃ to C₁₂, more preferablyC₅ to C₁₀, more preferably C₅, C₆ or C₇. Where acyclic, the alkyl groupis preferably C₁ to C₁₀, more preferably C₁ to C₆, more preferablymethyl, ethyl, propyl (n-propyl or isopropyl), butyl (n-butyl, isobutylor tertiary-butyl) or pentyl (including n-pentyl and iso-pentyl), morepreferably methyl. It will be appreciated therefore that the term“alkyl” as used herein includes alkyl (branched or unbranched), alkenyl(branched or unbranched), alkynyl (branched or unbranched), cycloalkyl,cycloalkenyl and cycloalkynyl.

As used herein, the term “lower alkyl” means methyl, ethyl, propyl(n-propyl or isopropyl) or butyl (n-butyl, isobutyl or tertiary-butyl).

As used herein, the term “aryl” means an aromatic group, such as phenylor naphthyl, or a heteroaromatic group containing one or moreheteroatom(s), such as pyridyl, pyrrolyl, quinolinyl, furanyl, thienyl,oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl,triazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.

As used herein, the term “heteroaryl” means an aromatic group containingone or more heteroatom(s) preferably selected from N, O and S, such aspyridyl, pyrrolyl, quinolinyl, furanyl, thienyl, oxadiazolyl,thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.

As used herein, the term “non-aromatic heterocyclyl” means anon-aromatic cyclic group containing one or more heteroatom(s)preferably selected from N, O and S, such as a cyclic amino group(including aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl,morpholinyl) or a cyclic ether (including tetrahydrofuranyl).

As used herein, the term “alkoxy” means alkyl-O—. As used herein, theterm “aryloxy” means aryl-O—.

As used herein, the term “halogen” means a fluorine, chlorine, bromineor iodine radical.

As used herein, the term “prodrug” means any pharmaceutically acceptableprodrug of a compound of the present invention.

Where any of R₁ to R₁₄ is selected from alkyl, alkoxy and alkylthio,particularly from alkyl and alkoxy, in accordance with formula (I) asdefined above, then that alkyl group, or the alkyl group of the alkoxyor alkylthio group, may be substituted or unsubstituted. Where any of R₁to R₁₄ is selected from aryl, aryloxy and arylthio, particularly fromaryl and aryloxy, in accordance with formula (I) as defined above, thensaid aryl group, or the aryl group of the aryloxy group, may besubstituted or unsubstituted. Where R₅ and R₆, or R₄ and R₅, are linkedto form a heterocyclic group, the heterocyclic group may be substitutedor unsubstituted. Where substituted, there will generally be 1 to 3substituents present, preferably 1 substituent. Substituents mayinclude:

-   carbon-containing groups such as    -   alkyl,    -   aryl, (e.g. substituted and unsubstituted phenyl (including        alkylphenyl, alkoxyphenyl and halophenyl),    -   arylalkyl; (e.g. substituted and unsubstituted benzyl);-   halogen atoms and halogen containing groups such as    -   haloalkyl (e.g. trifluoromethyl),    -   haloaryl (e.g. chlorophenyl);-   oxygen containing groups such as    -   alcohols (e.g. hydroxy, hydroxyalkyl, hydroxyaryl,        (aryl)(hydroxy)alkyl),    -   ethers (e.g. alkoxy, aryloxy, alkoxyalkyl, aryloxyalkyl,        alkoxyaryl, aryloxyaryl),    -   aldehydes (e.g. carboxaldehyde),    -   ketones (e.g. alkylcarbonyl, arylcarbonyl, alkylcarbonylalkyl,        alkylcarbonylaryl, arylcarbonylalkyl, arylcarbonylaryl,        arylalkylcarbonyl, arylalkylcarbonylalkyl,        arylalkylcarbonylaryl)    -   acids (e.g. carboxy, carboxyalkyl, carboxyaryl),    -   acid derivatives such as esters        -   (e.g. alkoxycarbonyl, aryloxycarbonyl, alkoxycarbonylalkyl,            aryloxycarbonylalkyl, alkoxycarbonylaryl,            aryloxycarbonylaryl, alkylcarbonyloxy,            alkylcarbonyloxyalkyl),        -   amides        -   (e.g. aminocarbonyl, mono- or di-alkylaminocarbonyl,            cyclicaminocarbonyl, aminocarbonylalkyl, mono- or            di-alkylaminocarbonylalkyl, arylaminocarbonyl or            arylalkylaminocarbonyl, alkylcarbonylamino,            arylcarbonylamino or arylalkylcarbonylamino),        -   carbamates        -   (eg. alkoxycarbonylamino, aryloxycarbonylamino,            arylalkyloxycarbonylamino, aminocarbonyloxy, mono- or            di-alkylaminocarbonyloxy, arylaminocarbonyloxy or            arylalkylaminocarbonyloxy)        -   and ureas        -   (eg. mono- or di-alkylaminocarbonylamino,            arylaminocarbonylamino or arylalkylaminocarbonylamino);-   nitrogen containing groups such as    -   amines (e.g. amino, mono- or dialkylamino, cyclicamino,        arylamino, aminoalkyl, mono- or dialkylaminoalkyl),    -   azides,    -   nitriles (e.g. cyano, cyanoalkyl),    -   nitro,    -   sulfonamides (e.g. aminosulfonyl, mono- or di-alkylamino        sulfonyl, mono- or di-arylaminosulfonyl, alkyl- or aryl-sulfonyl        amino, alkyl- or aryl-sulfonyl(alkyl)amino, alkyl- or        aryl-sulfonyl(aryl)amino);-   sulfur containing groups such as    -   thiols, thioethers, sulfoxides, and sulfones        -   (e.g. alkylthio, alkylsulfinyl, alkylsulfonyl,            alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,            arylthio, arylsulfinyl, arylsulfonyl, arylthioalkyl,            arylsulfinylalkyl, arylsulfonylalkyl)-   and heterocyclic groups containing one or more, preferably one,    heteroatom,    -   (e.g. thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl,        thiazolyl, isothiazolyl, oxazolyl, oxadiazolyl, thiadiazolyl,        aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl,        imidazolidinyl, imidazolinyl, pyrazolidinyl, tetrahydrofuranyl,        pyranyl, pyronyl, pyridyl, pyrazinyl, pyridazinyl, piperidyl,        hexahydroazepinyl, piperazinyl, morpholinyl, thianaphthyl,        benzofuranyl, isobenzofuranyl, indolyl, oxyindolyl, isoindolyl,        indazolyl, indolinyl, 7-azaindolyl, benzopyranyl, coumarinyl,        isocoumarinyl, quinolinyl, isoquinolinyl, naphthridinyl,        cinnolinyl, quinazolinyl, pyridopyridyl, benzoxazinyl,        quinoxalinyl, chromenyl, chromanyl, isochromanyl, phthalazinyl        and carbolinyl).

Where any of R₁ to R₁₄ is selected from aryl or from an aryl-containinggroup such as aryloxy or arylthio, preferred substituent group(s) areselected from halogen, alkyl (substituted or unsubstituted; and wheresubstituted particularly from alkoxyalkyl, hydroxyalkyl, aminoalkyl andhaloalkyl), hydroxy, alkoxy, CN, NO₂, amines (including amino, mono- anddi-alkylamino), alkoxycarbonyl, aminocarbonyl, carboxamido, sulfonamido,alkoxycarbonylamino and aryl, and particularly from unsubstituted alkyl,substituted alkyl (including alkoxyalkyl and aminoalkyl), halogen andamines.

In one embodiment, where any of R₁ to R₁₄ is directly substituted by analkyl substituent group, or by an alkyl-containing substituent group(such as alkoxy or alkylcarbonylamino for example), then the alkylmoiety of the substituent group directly attached to any of R₁ to R₁₄may be further substituted by the substituent groups hereinbeforedescribed and particularly by halogen, hydroxy, alkoxy, CN, amines(including amino, mono- and di-alkyl amino) and aryl.

In a further embodiment, where any of R₁ to R₁₄ is directly substitutedby an aryl substitutent group, or by an aryl-containing substituentgroup (such as aryloxy or arylaminocarbonylamino for example), then thearyl moiety of the substituent group directly attached to any of R₁ toR₁₄ may be further substituted by the substituent groups hereinbeforedescribed and particularly by halogen, alkyl (substituted orunsubstituted; and where substituted particularly from alkoxyalkyl,hydroxyalkyl, aminoalkyl and haloalkyl), hydroxy, alkoxy, CN, NO₂,amines (including amino, mono- and di-alkylamino), alkoxycarbonyl,aminocarbonyl, carboxamido, sulfonamido, alkoxycarbonylamino and aryl.In a further embodiment, said aryl moiety is substituted by halogen,alkyl (including CF₃), hydroxy, alkoxy, CN, amines (including amino,mono- and di-alkyl amino) and NO₂. In a further embodiment, said arylmoiety is substituted by unsubstituted alkyl, substituted alkyl(particularly alkoxyalkyl and aminoalkyl), halogen and amines.

The terms “directly substituted” and “directly attached”, as usedherein, mean that the substituent group is bound directly to any of R₁to R₁₄ without any intervening divalent atoms or groups.

In the compounds of formula (I), R₁ is selected from H, alkyl (includingbranched and unbranched alkyl, substituted and unsubstituted alkyl, andcyclic and acyclic alkyl), aryl (including heteroaryl), alkoxy, aryloxy,alkylthio, arylthio, halogen, CN, NR₅R₆ (including NH₂), NR₄COR₅,NR₄CONR₅R₆, N₄CO₂R₇ and NR₄SO₂R₇.

In one embodiment, the compounds of formula (I) are those wherein R₁ isselected from alkyl (including branched and unbranched alkyl,substituted and unsubstituted alkyl, and cyclic and acyclic alkyl), aryl(including heteroaryl), alkoxy, aryloxy, alkylthio, arylthio, halogen,CN, NR₅R₆ (including NH₂), NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇.

Preferably, R₁ is selected from alkyl (including branched and unbranchedalkyl, substituted and unsubstituted alkyl, and cyclic and acyclicalkyl), alkoxy, alkylthio, NR₅R₆ (including NH₂), NR₄COR₅, NR₄CONR₅R₆,NR₄CO₂R₇ and NR₄SO₂R₇, more preferably from NR₅R₆ (including NH₂),NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇, more preferably from NR₅R₆(including NH₂) and NR₄COR₅, more preferably from NR₅R₆ (including NH₂)and most preferably from NH₂.

Where R₁ is selected from NR₅R₆, in one embodiment R₅ and R₆ areindependently selected from hydrogen, alkyl and aryl, preferably fromhydrogen.

Where R₁ is selected from NR₄COR₅, in one embodiment R₄ is hydrogen.

Where R₁ is selected from alkyl, R₁ is preferably C₁₋₆ alkyl, morepreferably C₁₋₆ saturated alkyl, and more preferably lower alkyl. In oneembodiment, R₁ is selected from substituted alkyl, particularlyhaloalkyl (including CF₃) and arylalkyl (including heteroarylalkyl), andparticularly haloalkyl (including CF₃).

Preferably, R₂ is a heteroaryl group, and preferably a heteroaryl groupwhich is attached to the pyrimidine ring of formula (I) such that atleast one heteroatom is adjacent to the unsaturated carbon atom attachedto said pyrimidine ring. Preferably, R₂ is an N, O or S-containingheteroaryl group. R₂ may contain one or more heteroatom(s) selected fromN, O and S.

In one embodiment, the aryl group of R₂ (including wherein R₂ is aheteroaryl group) is not ortho, ortho-disubstituted. Preferably, thearyl group of R₂ (including wherein R₂ is a heteroaryl group) is notsubstituted at either ortho position. As used herein, reference toortho-substitution of the R₂ group means the ortho positions of the R₂group relative to the point of attachment of R₂ to the pyrimidine moietyof formula (I).

In a preferred embodiment, R₂ is selected from furyl (including2-furyl), thienyl (including 2-thienyl), pyridyl (including 2-pyridyl),thiazolyl (including 2- and 5-thiazolyl), pyrazolyl (including3-pyrazolyl), triazolyl (including 4-triazolyl), pyrrolyl (including2-pyrrolyl) and oxazolyl (including 5-oxazolyl). In a furtherembodiment, R₂ is selected from 2-furyl, 2-thienyl, 2-thiazolyl,2-pyridyl, 3-pyrazolyl, 2-pyrrolyl, 4-triazolyl and 5-oxazolyl. In afurther preferred embodiment, R₂ is selected from furyl, thienyl,pyridyl, thiazolyl and pyrazolyl, and particularly from 2-furyl,2-thienyl, 2-thiazolyl, 2-pyridyl and 3-pyrazolyl. In a furtherembodiment, R₂ is selected from furyl, thienyl and pyridyl, preferably2-furyl, 2-thienyl and 2-pyridyl. In a particularly preferredembodiment, R₂ is selected from furyl, and preferably from 2-furyl,substituted or unsubstituted.

Where R₂ is other than a heteroaryl group, R₂ is preferably phenyl.

In the compounds of formula (I), R₃ is selected from H, alkyl (includingbranched and unbranched alkyl, substituted and unsubstituted alkyl,cyclic and acyclic alkyl), COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆ and SO₂R₇.

Where R₃ is selected from alkyl, R₃ is preferably acyclic alkyl,preferably acyclic C₁₋₆ alkyl (including alkenyl and alkynyl),preferably acyclic C₁₋₆ saturated alkyl, preferably lower alkyl. In oneembodiment, R₃ is selected from substituted or unsubstituted methyl,ethyl and propyl (n-propyl or isopropyl) groups.

Where R₃ is selected from alkyl, particularly from saturated acyclicC₁₋₆ alkyl, particularly from lower alkyl and particularly from methyl,ethyl and propyl, it is preferred that R₃ is substituted alkyl.Preferred substituents are aryl (including heteroaryl), cycloalkyl,non-aromatic heterocyclyl, CN, COR₅, CO₂R₅, CONR₅R₆, CONR₄NR₅R₆ andC(═NR₄)NR₅R₆, preferably aryl (including heteroaryl), CONR₅R₆, CO₂R₅ andCOR₅ (preferably wherein R₅ is aryl), more preferably aryl (includingheteroaryl), CONR₅R₆ and CO₂R₅, more preferably aryl (includingheteroaryl) and CONR₅R₆, and most preferably aryl (includingheteroaryl).

Where R₃ is selected from arylalkyl (including heteroarylalkyl), thearyl (including heteroaryl) group may be unsubstituted, or substitutedas defined in detail below in respect of the group referred to as R₁₁.Preferably, the arylalkyl (including heteroarylalkyl group) is anarylmethyl (including heteroarylmethyl) group. The preferred aryl groupsare set out below in detail in respect of the group referred to as Ar.

Where R₃ is selected from CONR₅R₆, R₅ and R₆ are selected from H, alkyl(including substituted alkyl such as arylalkyl (includingheteroarylalkyl)) and aryl (including heteroaryl) or R₅ and R₆ may belinked to form a heterocyclic ring. In one embodiment, R₅ and R₆ areselected from unsubstituted alkyl and arylalkyl (includingheteroarylalkyl). Said aryl groups may be substituted or unsubstituted.In a preferred embodiment one of R₅ and R₆ is hydrogen. In a furtherpreferred embodiment, R₅ is H and R₆ is selected from arylalkyl(including heteroarylalkyl), preferably arylmethyl (includingheteroarylmethyl).

In a preferred embodiment, R₃ is selected from H and substituted alkyl,preferably wherein said alkyl is substituted by aryl (includingheteroaryl) or CONR₅R₆, and preferably by aryl (including heteroaryl),and more preferably by substituted aryl (including heteroaryl). In oneembodiment, R₃ is selected from (CR₉R₁₀)_(n)R₈ wherein n is 1 to 6(preferably n is 1, 2 or 3, and preferably n is 1), R₉ and R₁₀ areindependently selected from H, alkyl and aryl, and R₈ is selected fromaryl (including heteroaryl), cycloalkyl, non-aromatic heterocyclic, CN,COR₅, CO₂R₅, CONR₅R₆, CONR₄NR₅R₆ and C(═NR₄)NR₅R₆, preferably aryl(including heteroaryl), CONR₅R₆, CO₂R₅ and COR₅ (preferably wherein R₅is aryl), more preferably aryl (including heteroaryl), CONR₅R₆ andCO₂R₅, more preferably aryl (including heteroaryl) and CONR₅R₆, and mostpreferably aryl (including heteroaryl). Preferably, R₉ and R₁₀ areindependently selected from H and alkyl (preferably acyclic saturatedC₁₋₆ alkyl, preferably lower alkyl, preferably methyl, ethyl or propyl),more preferably H. Preferably, at least one of R₉ and R₁₀ is hydrogen,and preferably both R₉ and R₁₀ are hydrogen.

Where R₈ is aryl (including heteroaryl), the aryl (including heteroaryl)group may be unsubstituted, or may be substituted as defined in detailbelow for R₁₁. The preferred aryl groups are set out below in detail inrespect of the group referred to as Ar.

Where R₈ is selected from CONR₅R₆, R₅ and R₆ are selected from H, alkyl(including substituted alkyl such as arylalkyl (includingheteroarylalkyl)) and aryl (including heteroaryl) or R₅ and R₆ may belinked to form a heterocyclic ring. In one embodiment, one or both of R₅and R₆ are selected from unsubstituted alkyl and arylalkyl (includingheteroarylalkyl). In a further embodiment, at least one of R₅ and R₆ isselected from aryl (including heteroaryl). Said aryl group may besubstituted or unsubstituted. In a preferred embodiment, one of R₅ andR₆ is hydrogen.

Where R₈ is selected from COR₅, R₅ is preferably aryl (includingheteroaryl).

Where R₈ is selected from CO₂R₅, R₅ is preferably alkyl or aryl.

In a further preferred embodiment, R₃ is selected from H and(CR₉R₁₀)_(n)R₈, more preferably from (CH₂)_(n)R₈, preferably wherein R₈is selected from aryl (including heteroaryl) and CONR₅R₆, morepreferably wherein R₈ is selected from aryl (including heteroaryl), andmore preferably wherein R₈ is selected from substituted aryl (includingheteroaryl).

In a further embodiment, R₃ is selected from (CR₉R₁₀)_(n)R₁₁ wherein R₉,R₁₀ and n are as defined above and R₁₁ is selected from the groupconsisting of substituted aryl (including heteroaryl) groups, preferablymono-, di- or tri-substituted aryl (including heteroaryl) groupsrepresented by the formula Ar(R₁₂)_(a)(R₁₃)_(b)(R₁₄)_(c) wherein Ar isan aryl (including heteroaryl) group; wherein R₁₂, R₁₃ and R₁₄ aresubstituent group(s), the same or different; and wherein a, b and c are0 or 1 such that a+b+c≧1.

In one embodiment, the group Ar is selected from phenyl. In analternative embodiment, the group Ar is selected from heteroaryl groupssuch as those described hereinabove, preferably from mono or bicyclicheteroaryl groups, more preferably from pyridyl (including 2-pyridyl,3-pyridyl and 4-pyridyl, preferably 2-pyridyl), indolyl (including2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl and 7-indolyl),furyl (including 2-furyl and 3-furyl, preferably 2-furyl), thienyl(including 2-thienyl and 3-thienyl, preferably 2-thienyl), isoindolyl,indolinyl, isoxazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrimidinyl,quinolinyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl,indazolyl, benzodioxolyl and dihydrobenzofuranyl, more preferably frompyridyl (preferably 2-pyridyl), indolyl, furyl (preferably 2-furyl) andthienyl (preferably 2-thienyl), and most preferably from pyridyl(preferably 2-pyridyl), furyl (preferably 2-furyl) and thienyl(preferably 2-thienyl).

In one embodiment, the group Ar is selected from phenyl, pyridyl(preferably 2-pyridyl), furyl (preferably 2-furyl), thienyl (preferably2-thienyl) and indolyl, and particularly from phenyl, pyridyl(preferably 2-pyridyl), furyl (preferably 2-furyl) and thienyl(preferably 2-thienyl).

The substituent groups R₁₂, R₁₃ and R₁₄ may be selected from any of thesubstituent groups described herein above.

In a preferred embodiment, R₁₂, R₁₃ and R₁₄ are selected from NR₅R₆(including NH₂, and NHR₅) alkyl (substituted or unsubstituted;preferably C₁₋₆ acyclic alkyl), alkoxy (including fluoroalkoxy), halogen(including F, Cl, Br and I), NO₂, CN, hydroxy, NHOH, CHO, CONR₅R₆,CO₂R₅, NR₄COR₅ (preferably NHCOR₅), NR₄CO₂R₇ (preferably NHCO₂R₇),NR₄SO₂R₇ (preferably NHSO₂R₇), OCO₂R₇ and aryl (including heteroaryl).

In a more preferred embodiment, R₁₂, R₁₃ and R₁₄ are selected from NR₅R₆(including NH₂ and NHR₅), alkyl (substituted or unsubstituted; andpreferably C₁₋₆ acyclic saturated alkyl) and halogen (preferably F orCl, particularly F).

In a particularly preferred embodiment, R₁₂, R₁₃ and R₁₄ are selectedfrom NR₅R₆ (including NH₂ and NHR₅, preferably NH₂) and alkyl(substituted or unsubstituted; preferably C₁₋₆ acyclic saturated alkyl).

Where R₁₂, R₁₃ and R₁₄ are selected from substituted alkyl, said alkylis preferably selected from alkoxyalkyl, hydroxyalkyl, aminoalkyl(including NH₂-alkyl, mono-alkylaminoalkyl and di-alkylaminoalkyl),haloalkyl (particularly fluoroalkyl (including CF₃)), cyanoalkyl,alkylthioalkyl, alkylcarboxyaminoalkyl, alkoxycarbonylaminoalkyl andalkylsulfonylamino, more preferably from alkoxyalkyl, hydroxyalkyl,aminoalkyl and haloalkyl (particularly fluoroalkyl (including CF₃)) andmost preferably from alkoxyalkyl and aminoalkyl.

In one embodiment, the substituent groups R₁₂, R₁₃ and R₁₄ are selectedfrom halogen, alkyl (including CF₃), hydroxy, alkoxy, alkylthio, CN,amines (including amino, mono- and di-alkyl amino) and NO₂.

Where the Ar group is phenyl, the phenyl ring may be mono-, di- ortri-substituted, preferably wherein the substituent group is selectedfrom NR₅R₆, alkyl, alkoxy, halogen, NO₂, CN, hydroxy, CONR₅R₆, CO₂R₅,NR₄COR₅, NR₄CO₂R₇, NR₄SO₂R₇ and OCO₂R₇, as described above, and morepreferably from NR₅R₆ (including NH₂ and NHR₅, and preferably NH₂),alkyl (substituted or unsubstituted; preferably C₁₋₆ acyclic saturatedalkyl; and, where substituted, preferably from alkoxyalkyl,hydroxyalkyl, aminoalkyl and haloalkyl (particularly fluoroalkyl(including CF₃)), and more preferably from alkoxyalkyl and aminoalkyl)and halogen (preferably F or Cl, particularly F). Where (a+b+c) is 2 or3, it is preferred that at least one of the substituent groups is NR₅R₆,particularly NH₂.

Where the Ar group is pyridyl, the pyridyl group (which is preferably a2-pyridyl group) is preferably mono-substituted, preferably6-substituted. The preferred substituent group(s) are selected fromalkyl (including substituted and unsubstituted, saturated andunsaturated (such as alkenyl, including vinyl); and preferably C₁₋₆acyclic alkyl), alkoxy, halogen, aryl, NO₂, NHOH and CHO, as describedabove, and more preferably from alkyl (substituted or unsubstituted;preferably C₁₋₆ acyclic saturated alkyl; and, where substituted,preferably from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl(particularly fluoroalkyl (including CF₃)), and more preferably fromalkoxyalkyl and aminoalkyl).

In a preferred embodiment R₃ is selected from CHR₉R₁₁ wherein R₉ and R₁₁are as defined above, and preferably wherein Ar is substituted pyridylor substituted phenyl. Where Ar is substituted phenyl, preferably atleast one of R₁₂ and R₁₃, or at least one of R₁₂, R₁₃ and R₁₄, is NR₅R₆,preferably NH₂.

In the compounds of formula (I), R₄, R₅ and R₆ are independentlyselected from H, alkyl (including branched and unbranched alkyl,substituted and unsubstituted alkyl, cyclic and acyclic alkyl) and aryl(including heteroaryl) or where R₅ and R₆ are in any NR₅R₆ group, R₅ andR₆ may be linked to form a heterocyclic ring, or where R₄, R₅ and R₆ arein a (CONR₄NR₅R₆) group, R₄ and R₅ may be linked to form a heterocyclicring.

In the compounds of formula (I), R₇ is selected from alkyl (includingbranched and unbranched alkyl, substituted and unsubstituted alkyl,cyclic and acyclic alkyl) and aryl (including heteroaryl).

Where R₄ to R₇ are independently selected from alkyl, preferably R₄ toR₇ are selected from C₁₋₆ alkyl, preferably C₁₋₆ saturated alkyl andmore preferably from lower alkyl.

Where R₅ and R₆, or R₄ and R₅, are linked to form a heterocyclic ringsaid heterocyclic ring may be saturated, partially unsaturated oraromatic, and is preferably saturated. Said heterocyclic ring ispreferably a 5, 6 or 7-membered ring, preferably a 5 or 6-membered ring,and may contain one or more further heteroatom(s) preferably selectedfrom N, O and S.

In a preferred embodiment, R₁ is NH₂, R₂ is 2-furyl and R₃ is arylmethyl(including heteroarylmethyl).

In one embodiment of the invention, the compounds of formula (I) areselected from those set out in claim 41.

In a further embodiment of the invention, the compounds of formula (I)are selected from those set out in claim 42.

Where chiral the compounds of formula (I) may be in the form of aracemic mixture of pairs of enantiomers or in enantiomerically pureform.

According to a further aspect of the present invention there is provideda method of treating or preventing a disorder in which the blocking ofpurine receptors, particularly adenosine receptors and more particularlyadenosine A_(2A) receptors, may be beneficial, the method comprisingadministration to a subject in need of such treatment an effective doseof a compound of formula (I) or a pharmaceutically acceptable salt orprodrug thereof.

The disorder may be caused by the hyperfunctioning of the purinereceptors.

The disorders of particular interest are those in which the blocking ofpurine receptors, particularly adenosine receptors and more particularlyadenosine A_(2A) receptors, may be beneficial. These may includemovement disorders such as Parkinson's disease, drug-inducedParkinsonism, post-encephalitic Parkinsonism, Parkinsonism induced bypoisoning (for example MPTP, manganese, carbon monoxide) andpost-traumatic Parkinson's disease (punch-drunk syndrome).

Other movement disorders in which the blocking of purine receptors, maybe of benefit include progressive supernuclear palsy, Huntington'sdisease, multiple system atrophy, corticobasal degeneration, Wilsonsdisease, Hallerrorden-Spatz disease, progressive pallidal atrophy,Dopa-responsive dystonia-Parkinsonism, spasticity or other disorders ofthe basal ganglia which result in abnormal movement or posture. Thepresent invention may also be effective in treating Parkinson's withon-off phenomena; Parkinson's with freezing (end of dose deterioration);and Parkinson's with prominent dyskinesias.

The compounds of formula (I) may be used or administered in combinationwith one or more additional drugs useful in the treatment of movementdisorders, such as L-DOPA or a dopamine agonist, the components being inthe same formulation or in separate formulations for administrationsimultaneously or sequentially.

Other disorders in which the blocking of purine receptors, particularlyadenosine receptors and more particularly adenosine A_(2A) receptors maybe beneficial include acute and chronic pain; for example neuropathicpain, cancer pain, trigeminal neuralgia, migraine and other conditionsassociated with cephalic pain, primary and secondary hyperalgesia,inflammatory pain, nociceptive pain, tabes dorsalis, phantom limb pain,spinal cord injury pain, central pain, post-herpetic pain and HIV pain;affective disorders including mood disorders such as bipolar disorder,seasonal affective disorder, depression, manic depression, atypicaldepression and monodepressive disease; central and peripheral nervoussystem degenerative disorders including corticobasal degeneration,demyelinating disease (multiple sclerosis, disseminated sclerosis),Freidrich's ataxia, motoneurone disease (amyotrophic lateral sclerosis,progressive bulbar atrophy), multiple system atrophy, myelopathy,radiculopathy, peripheral neuropathy (diabetic neuropathy, tabesdorsalis, drug-induced neuropathy, vitamin deficiency), systemic lupuserythamatosis, granulomatous disease, olivo-ponto-cerebellar atrophy,progressive pallidal atrophy, progressive supranuclear palsy,spasticity; schizophrenia and related pyshoses; cognitive disordersincluding dementia, Alzheimer's Disease, Frontotemporal dementia,multi-infarct dementia, AIDS dementia, dementia associated withHuntington's Disease, Lewy body dementia, senile dementia, age-relatedmemory impairment, cognitive impairment associated with dementia,Korsakoff syndrome, dementia pugilans; attention disorders such asattention-deficit hyperactivity disorder (ADHD), attention deficitdisorder, minimal brain dysfunction, brain-injured child syndrome,hyperkinetic reaction childhood, and hyperactive child syndrome; centralnervous system injury including traumatic brain injury, neurosurgery(surgical trauma), neuroprotection for head injury, raised intracranialpressure, cerebral oedema, hydrocephalus, spinal cord injury; cerebralischaemia including transient ischaemic attack, stroke (thromboticstroke, ischaemic stroke, embolic stroke, haemorrhagic stroke, lacunarstroke) subarachnoid haemorrhage, cerebral vasospasm, neuroprotectionfor stroke, peri-natal asphyxia, drowning, cardiac arrest, subduralhaematoma; myocardial ischaemia; muscle ischaemia; sleep disorders suchas hypersomnia and narcolepsy; eye disorders such as retinalischaemia-reperfusion injury and diabetic neuropathy; cardiovasculardisorders such as claudication and hypotension; and diabetes and itscomplications.

According to a further aspect of the present invention there is provideduse of a compound of formula (I) or a pharmaceutically acceptable saltor prodrug thereof in the manufacture of a medicament for the treatmentor prevention of movement disorders in a subject.

According to a further aspect of the invention there is provided amethod of treating or preventing movement disorders comprisingadministration to a subject in need of such treatment an effective doseof a compound of formula (I) invention or a pharmaceutically acceptablesalt or prodrug thereof.

According to a further aspect of the invention there is provided use ofa compound of formula (I) or a pharmaceutically acceptable salt orprodrug thereof in the manufacture of a medicament for neuroprotectionin a subject.

According to a further aspect of the invention there is provided amethod of neuroprotection comprising administration to a subject in needof such treatment an effective dose of a compound of formula (I) or apharmaceutically acceptable salt or prodrug thereof.

The medicament for or method of neuroprotection may be of use in thetreatment of subjects who are suffering from or at risk from aneurodegenerative disorder, such as a movement disorder.

According to a further aspect of the invention, there is provided foruse in therapy a compound of formula (I), or a pharmaceuticallyacceptable salt or prodrug thereof.

The present invention may be employed in respect of a human or animalsubject, more preferably a mammal, more preferably a human subject.

According to a further aspect of the present invention, there isprovided a compound of formula (I), per se, other than compounds whereinR₁ is H and R₃ is selected from methyl, more preferably other thancompounds wherein R₁ is H and R₃ is selected from unsubstituted loweralkyl, more preferably other than compounds wherein R₁ is H and R₃ isselected from unsubstituted alkyl, and more preferably other thancompounds wherein R₁ is H.

According to a further aspect of the present invention, there isprovided a compound of formula (I), per se, other than compounds whereinR₃ is methyl, preferably other than compounds wherein R₃ isunsubstituted lower alkyl and more preferably other than compoundswherein R₃ is unsubstituted alkyl.

According to a further aspect of the invention there is provided amethod of preparing the novel compounds of formula (1). Compounds offormula (1) may be prepared according to conventional synthetic methods.For example compounds of formula (1) where R₁ is NH₂ may be synthesisedby standard methods such as those illustrated in Reaction Scheme 1.

Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (3) by standard methods such as reaction with an appropriatealkyl halide, or substituted alkyl halide in the presence of a suitablebase such as sodium hydride.

Compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)CONR₅R₆ or(CR₉R₁₀)_(n)CONR₄NR₅R₆ may be prepared from compounds of formula (4)where R₃ is (CR₉R₁₀)_(n)CO₂R₅ by standard methods such as directreaction with an appropriate amine or hydrazine or by initial hydrolysisof the ester group CO₂R₅ to a carboxylic acid followed by reaction withan appropriate amine or hydrazine in the presence of a standard couplingreagent such as DCC.

Compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)C(═NR₄)NR₅R₆ may beprepared from compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)CN bystandard methods such as treatment with an appropriate amine in thepresence of trimethyl aluminium.

Compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)CN may be prepared fromcompounds of formula (3) by standard methods such as treatment with anappropriate substituted alkyl halide in the presence of a suitable basesuch as sodium hydride.

Compounds of formula (4) where R₃ is CONR₅R₆ or CONR₄NR₅R₆ may beprepared from compounds of formula (3) by standard methods such astreatment with an appropriate isocyanate (R₅NCO or R₆NCO) or carbamoylchloride (R₅R₆NCOCl or R₅R₆NR₄NCOCl).

Compounds of formula (4) where R₃ is COR₅, CO₂R₇ or SO₂R₇ may beprepared from compounds of formula (3) by standard methods such astreatment with an appropriate acid chloride (R₅COCl), chloroformate(ClCO₂R₇) or sulphonyl chloride (R₇SO₂Cl) in the presence of a suitablebase such as triethylamine.

Compounds of formula (3) may be prepared from the known chloro compoundof formula (2) by standard methods such as aryl or heteroaryl couplingreactions. Suitable aryl or heteroaryl coupling reactions would includereaction with an appropriate aryl or heteroarylboronic acid derivative,an aryl or heteroaryl trialkylstannane derivative or an aryl orheteroarylzinc halide derivative in the presence of a suitable catalystsuch as a palladium complex.

Compounds of formula (3) may also be prepared from compounds of formula(7) by standard methods such as treatment with isoamyl nitrite.Compounds of formula (7) are either known in the literature or may beprepared from compounds of formula (6) by standard methods such asreduction with hydrogen in the presence of a suitable catalyst such asPd. Compounds of formula (6) are either known in the literature or maybe prepared from the known compound of formula (5) by standard methodssuch as aryl or heteroaryl coupling reactions as described above.

Compounds of formula (1) where R₁ is NR₅R₆ may be prepared fromcompounds of formula (4) by standard methods such as reductive aminationwith an appropriate aldehyde or ketone, or by treatment with anappropriate alkyl halide in the presence of a suitable base.

Compounds of formula (1) where R₁ is NR₄CONR₅R₆, wherein R₄ is H, may beprepared from compounds of formula (4) by standard methods such astreatment with an appropriate isocyanate (R₅NCO or R₆NCO) or carbamoylchloride (R₅R₆NCOCl). Compounds of formula (1) where R₁ is NR₄CONR₅R₆,wherein R₄ is alkyl, may be prepared as described above having firstperformed an additional alkylation step as described above.

Compounds of formula (1) where R₁ is NR₄COR₅, NR₄CO₂R₇ or NR₄SO₂R₇,wherein R₄ is H, may be prepared from compounds of formula (4) bystandard methods such as treatment with an appropriate acid chloride(R₅COCl), chloroformate (ClCO₂R₇) or sulphonyl chloride (R₇SO₂Cl) in thepresence of a suitable base. Compounds of formula (1) where R₁ isNR₄COR₅, NR₄CO₂R₇ or NR₄SO₂R₇, wherein R₄ is alkyl, may be prepared asdescribed above having first performed an additional alkylation step asdescribed above.

Compounds of formula (1) where R₁ is NH₂ may also be synthesised bystandard methods such as those illustrated in Reaction Scheme 2.

Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (10) by standard methods such as aryl or heteroaryl couplingreactions as described above. Compounds of formula (10) where R₃ isalkyl are either known in the literature or may be prepared by methodsanalogous to those described in the literature. For example compounds offormula (10) where R₃ is alkyl may be prepared from compounds of formula(9) where R₃ is alkyl by standard methods such as treatment with isoamylnitrite. Compounds of formula (9) where R₃ is alkyl are either known inthe literature or may be prepared by methods analogous to thosedescribed in the literature such as the treatment of the known compoundof formula (8) with an appropriate amine in a suitable solventpreferably at elevated temperature.

Compounds of formula (1) where R₁ is NH₂ may also be synthesised bystandard methods such as those illustrated in Reaction Scheme 3.

Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (15) where R₃ is alkyl by standard methods such as treatmentwith isoamyl nitrite. Compounds of formula (15) where R₃ is alkyl may beprepared from compounds of formula (14) where R₃ is alkyl by standardmethods such as reduction with hydrogen in the presence of a suitablecatalyst such as Pd. Compounds of formula (14) where R₃ is alkyl areeither known in the literature or may be prepared from compounds offormula (13), where X is a suitable leaving group such as a tosylate ortriflate group, by standard methods such as treatment with a suitableamine in the presence of a suitable base such as triethylamine.Compounds of formula (13) where X is a suitable leaving group are eitherknown in the literature or may be prepared from compounds of formula(12) by standard methods such as treatment with tosyl chloride ortriflic anhydride in the prence of a suitable base such as triethylamineor 2,6-dimethylpyridine. Compounds of formula (12) are either known inthe literature or may be prepared from the known compound of formula(11) by standard methods such as aryl or heteroaryl coupling reactionsas described above.

Other compounds of formula (1) may be prepared by standard methods suchas those illustrated in Reaction Scheme 4.

Compounds of formula (1) where R₁ is H, alkyl or aryl may be preparedfrom compounds of formula (16) where R₁ is H, alkyl or aryl by standardmethods such as aryl or heteroaryl coupling reactions as describedabove. Compounds of formula (16) where R₁ is H, alkyl or aryl are eitherknown in the literature or may be prepared by methods analogous to thosedescribed in the literature.

Compounds of formula (1) where R₁ is alkoxy, aryloxy, alkylthio,arylthio, CN or NR₅R₆ may be prepared from compounds of formula (1)where R₁ is halogen by standard methods such as nucleophilicdisplacement using an appropriate nucleophilic reagent such as analcohol, thiol, cyanide or amine (HNR₅R₆) in the presence of a suitablebase if required. Compounds of formula (1) where R₁ is halogen may beprepared from compounds of formula (16) where R₁ is halogen as describedabove. Compounds of formula (16) where R₁ is halogen are either known inthe literature or may be prepared by methods analogous to thosedescribed in the literature.

Compounds of formula (1) where R₁ is NR₄CONR₅R₆, NR₄COR₅, NR₄CO₂R₇ orNR₄SO₂R₇, wherein R₄ is alkyl or aryl, may be prepared from compounds offormula (1) where R₁ is NR₅R₆, wherein R₅ is H and R₆ is alkyl or aryl,by the methods described above.

In certain cases it may be advantageous to prepare a compound of formula(1) where R₃ is selected to perform the function of a protecting group,for example a suitable protecting group would be a benzyl group orsubstituted benzyl group such as a 3,4-dimethoxybenzyl group. Compoundsof this nature may prepared as described above and the protecting groupR₃ may be removed by standard methods such as treatment with, forexample, TFA to give a compound of formula (1) where R₃ is H. Compoundsof formula (1) where R₃ is H may then be used to prepare other compoundsof formula (1), where R₃ is as previously defined, by the methodsdescribed above.

In the compounds of formula (1) the groups R₁, R₂ and R₃ may be furthersubstituted as defined above and it will be appreciated by those skilledin the art that suitable substituent groups may be introduced directlyaccording to the methods described above or alternatively may beintroduced by further functionalisation of substituent groups whichthemselves are introduced directly. For example where the group R₁, R₂or R₃ contains a nitro substituent this may be reduced by standardmethods to an amino group. The resulting amino group may then be furthertransformed by a variety of standard methods known to those skilled inthe art to an alternative functional group such as an amide, urea,carbamate, sulphonamide or alkylamine.

According to a further aspect of the invention, there is provided apharmaceutical composition comprising a compound of formula (I) incombination with a pharmaceutically acceptable carrier or excipient anda method of making such a composition comprising combining a compound offormula (I) with a pharmaceutically acceptable carrier or excipient.

The pharmaceutical compositions employed in the present inventioncomprise a compound of the present invention, or pharmaceuticallyacceptable salts or prodrugs thereof, and may also contain apharmaceutically acceptable carrier and optionally other therapeuticingredients known to those skilled in the art. The term,“pharmaceutically acceptable salts”, refers to salts prepared frompharmaceutically acceptable non-toxic acids including inorganic acidsand organic acids.

Where the compounds of formula (I) are basic, salts may be prepared frompharmaceutically acceptable non-toxic acids including inorganic andorganic acids. Such acids include acetic, benzenesulfonic, benzoic,camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic, glutamic,hippuric, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic,mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic,phosphoric, succinic, sulfuric, tartaric, oxalic, p-toluenesulfonic andthe like. Particularly preferred are hydrochloric, hydrobromic,phosphoric, and sulfuric acids, and most particularly preferred is thehydrochloride salt.

Any suitable route of administration may be employed for providing thepatient with an effective dosage of a compound of the present invention.For example, oral, rectal, parenteral (intravenous, intramuscular),transdermal, subcutaneous, and the like may be employed. Dosage formsinclude tablets, troches, dispersions, suspensions, solutions, capsules,patches, and the like. The most suitable route in any given case willdepend on the severity of the condition being treated. The mostpreferred route of administration of the present invention is the oralroute. The compositions may be conveniently presented in unit dosageform and prepared by any of the methods well known in the art ofpharmacy.

In practical use, the compounds can be combined as the active ingredientin intimate admixture with a pharmaceutical carrier according toconventional pharmaceutical compounding techniques. The carrier may takea wide variety of forms depending on the form of preparation desired foradministration, e.g. oral or parenteral (e.g. intravenous). In preparingthe compositions for oral dosage form, any of the usual pharmaceuticalmedia may be employed as carriers, such as, for example, water, glycols,oils, alcohols, flavouring agents, preservatives, colouring agents, andthe like in the case of oral liquid preparations (such as suspensions,solutions and elixirs) or aerosols; or carriers such as starches,sugars, micro-crystalline cellulose, diluents, granulating agents,lubricants, binders, disintegrating agents, and the like may be used inthe case of oral solid preparations such as, for example, powders,capsules, and tablets, with the solid oral preparations being preferredover the liquid preparations. The most preferred solid oral preparationis tablets.

Because of their ease of administration, tablets and capsules representthe most advantageous oral dosage unit form in which case solidpharmaceutical carriers are employed. If desired, tablets may be coatedby standard aqueous or non-aqueous techniques.

In addition to the common dosage forms set out above, the compounds mayalso be administered by controlled release means and/or delivery devicessuch as those described in U.S. Pat. Nos. 3,845,770; 3,916,899;3,536,809; 3,598,123; 3,630,200; 4,008,719; 4,687,660; and 4,769,027,the disclosures of which are hereby incorporated by reference.

Pharmaceutical compositions employed in the present invention suitablefor oral administration may be presented as discrete units such ascapsules, cachets, or tablets, or aerosol sprays each containing apredetermined amount of the active ingredient as a powder or granules, asolution or a suspension in an aqueous liquid, an oil-in-water emulsion,or a water-in-oil liquid emulsion. Such compositions may be prepared byany of the methods of pharmacy, but all methods include the step ofbringing the active ingredient into association with the carrier whichconstitutes one or more necessary ingredients. In general, thecompositions are prepared by uniformly and intimately admixing theactive ingredient with liquid carriers or finely divided solid carriersor both, and then, if necessary, shaping the product into the desiredpresentation.

For example, a tablet may be prepared by compression or moulding,optionally with one or more accessory ingredients. Compressed tabletsmay be prepared by compressing in a suitable machine the activeingredient in a free-flowing form such as powder or granules, optionallymixed with a binder, a lubricant, an inert diluent, and/or a surfaceactive or dispersing agent. Moulded tablets may be made by moulding in asuitable machine a mixture of the powdered compound moistened with aninert liquid diluent.

The invention is further defined by reference to the following examples.It will be apparent to those skilled in the art that many modifications,both to materials and methods, may be practised without departing fromthe purpose and interest of this invention.

EXAMPLES Synthetic Examples

The invention is illustrated with reference to the following Examples,as set out in Table 1.

TABLE 1 Example Structure Compound Name 1

7-(2-furyl)-1H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 2

N,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine- 5-amine 3

3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 4

7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 5

3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 6

methyl 3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methylbenzoate 7

3-(3,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 8

3-(5-chloro-2-thienyl)methyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 9

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4- yl)sulphonamide 10

5-amino-N-benzyl-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide 11

7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 12

7-(2-furyl)-3-(2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 13

3-(2-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 14

ethyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate 15

3-(3-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 16

7-(2-furyl)-3-(3-(3-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 17

7-(2-furyl)-3-(3-trifluoromethylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 18

7-(2-furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 19

7-(5-methyl-2-furyl)-1H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 20

3-(2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 21

7-(1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 22

3-(2-fluorobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 23

7-(2-furyl)-3-(3-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 24

7-(2-furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 25

7-(2-furyl)-3-(3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 26

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidin-3-yl)aceticacid 27

3-(3-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 28

3-(2-fluorobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 29

7-(2-furyl)-3-methyl-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 30

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidin-3-yl)acetamide31

(5-amino-7-(2-furyl)-3H-[1,2,3]triazole[4,5- d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide 32

7-(2-furyl)-3-(6-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 33

7-(2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 34

3-(2-fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 35

3-(2-fluorobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 36

3-(3-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 37

7-(2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 38

3-(2-fluorobenzyl)-7-(5-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 39

tert-butyl N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 40

3-(2,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 41

3-(2,6-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 42

3-(2-fluorobenzyl)-7-(4-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 43

7-(2-thienyl)-1H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 44

6-chloro-N-(7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine- 3-carboxamide 45

3-(3-nitrobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 46

3-(3-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 47

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-N,N- dimethylbenzamide 48

3-(3-aminobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 49

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-methylbenzamide 50

3-(3-aminobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 51

3-(2-fluoro-5-methyoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 52

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridyl)acetamide 53

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidin-3-yl)-N-(2-pyridylmethyl)acetamide 54

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-phenylacetamide 55

3-(3,5-dinitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 56

7-(5-methyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 57

3-(2,3-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 58

3-(2,4-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 59

7-(5-methyl-2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 60

3-(2,6-difluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 61

7-(5-methyl-2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 62

3-(3-chlorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 63

7-(2-furyl)-3-(4-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 64

7-(2-furyl)-3-(2-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 65

3-(2,5-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 66

7-(2-furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 67

3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)- N-methylbenzamide 68

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 69

3-(2-fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 70

3-(4-chloro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 71

3-(6-fluoro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 72

3-(2-methyoxybenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 73

tert-butyl N-(3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 74

3-(2-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 75

3-(3,5-diaminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 76

3-(3-aminomethylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine hydrochloride 77

7-(2-furyl)-3-(2-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 78

3-(2-fluoro-5-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 79

3-(5-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 80

3-(2-fluorobenzyl)-7-(1H-triazol-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 81

3-(6-chloro-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 82

7-(5-methyl-2-furyl)-3-(6-phenyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 83

3-(3-aminobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 84

3-(5-amino-2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine hydrochloride 85

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)-3-methylbutanamide 86

7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 87

3-(4-hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 88

7-(2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 89

3-(3-amino-2-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 90

3-(3-amino-4-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 91

3-(3,5-dimethylisoxazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 92

7-(2-furyl)-3-(3-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 93

3-cyclohexylmethyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 94

7-(2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 95

7-(2-furyl)-3-(3-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 96

7-(2-furyl)-3-(5-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 97

3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 98

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzoic acid 99

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzamide 100

7-(2-furyl)-3-(2-methylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 101

3-(3-aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 102

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropyl-N- methylbenzamide 103

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N- isopropylbenzamide 104

3-(2-amino-5-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 105

3-(4-cyano-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 106

7-(2-furyl)-3-(5-methyl-2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 107

7-(2-furyl)-3-(8-quinolinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 108

7-(2-furyl)-3-(2-phenylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 109

7-(4-methyl-2-thiazolyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 110

3-(4-chloro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 111

3-(1,2,5-benzoxadiazol-5-yl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 112

7-(2-furyl)-3-(6-methoxymethyl-2- pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 113

3-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 114

3-(3-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 115

7-(2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 116

7-(2-furyl)-3-(4-hydroxylamino-2- pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 117

7-(2-furyl)-3-(6-methyl-4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 118

7-(2-furyl)-3-(4-hydroxylamino-6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 119

3-(4-chloro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 120

3-(2-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 121

3-(4-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 122

3-(3,4-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine trifluoroacetate salt 123

7-(5-methyl-2-furyl)-3-(3-methyl-4- nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 124

3-(4-amino-3-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 125

7-(2-furyl)-3-(5-methyl-3-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 126

7-(2-furyl)-3-(3-methyl-4-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 127

3-(1,2,5-benzothiadiazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 128

7-(2-furyl)-3-(2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 129

3-(4-fluoro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 130

3-(3-nitrobenzyl)-7-phenyl-3H- [1,2,3]triazolo[4,5-d]pyrimidine-5-amine131

7-(2-furyl)-3-(4-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 132

tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 4-pyridylmethyl)carbamate133

7-(2-furyl)-3-(3-methoxy-4-nitrobenzyl)-3H[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 134

7-(2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 135

3-(6-ethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 136

3-(2-ethyl-4-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 137

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 138

tert-butyl 4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 139

7-(2-furyl)-3-(4-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 140

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 141

3-(4-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 142

tert-butyl 5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 143

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 2-fluorophenyl)carbamate144

3-(4-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 145

7-(5-ethyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 146

tert-butyl 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 147

3-(4-amino-3-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 148

tert-butyl (4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-3,5-difluorophenyl)carbonate 149

3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 150

3-(3-aminobenzyl)-7-(5-ethyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 151

3-(3-aminobenzyl)-7-phenyl-3H- [1,2,3]triazolo[4,5-d]pyrimidine-5-amine152

7-(2-furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 153

7-(2-furyl)-3-(5-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 154

7-(2-furyl)-3-(7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 155

3-(5-fluoro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 156

3-(2,6-difluoro-4-methyoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 157

tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate 158

3-(1H-benzotriazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 159

7-(2-furyl)-3-(2-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 160

N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenylacetamide 161

3-(2-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 162

3-(3-(N,N-dimethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 163

3-(4-difluoromethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 164

7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 165

3-(3-amino-4-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 166

3-(2,3-dihydrobenzofuran-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 167

3-(5-bromo-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 168

7-(2-furyl)-3-(2,3,5-trifluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 169

3-(2-fluoro-5-iodobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 170

7-(2-furyl)-3-(2-furylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 171

3-(2-amino-5-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 172

tert-butyl (5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 2-nitrophenyl)carbonate173

3-(4-amino-3-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 174

3-(4-amino-3-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 175

3-(3-aminobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 176

7-(2-furyl)-3-(3-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 177

N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- pyridylmethyl)acetamide178

N-(2-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 179

7-(2-furyl)-3-(3-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 180

3-(3-amino-2-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 181

7-(2-furyl)-3-(3-methyl-2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 182

3-(6-allyloxymethyl-2-pyridylmethyl)- N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 183

3-(6-methoxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 184

3-(4-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 185

3-(6-allyloxymethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 186

3-(6-allyloxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 187

7-(2-furyl)-3-(3-isopropyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 188

7-(2-furyl)-3-(quinolin-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 189

7-(2-furyl)-3-(4-(N-methylamino)benzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 190

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(6-methyl-2- pyridyl)propanone 191

3-(3-aminobenzyl)-7-(1H-pyrrol-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 192

3-(3-nitrobenzyl)-7-(2-pyridyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 193

N-(4-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)acetamide 194

7-(2-furyl)-3-(4-nitro-2-(2- trimethylsilylethoxy)methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 195

3-(3-ethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 196

7-(2-furyl)-3-(2-(2-thienylethyl))-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 197

7-(2-furyl)-3-(6-isopropyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 198

7-(2-furyl)-3-(1-(2H-tetrahyropyran-2-yl)indazol-5-ylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 199

3-(4,6-diisopropyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 200

7-(2-furyl)-3-(5-indazolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 201

7-(2-furyl)-3-(2-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 202

7-(2-furyl)-3-(6-vinyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 203

tert-butyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate 204

tert-butyl 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 205

6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2- carboxaldehyde 206

tert-butyl 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 207

3-(2-indolylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 208

3-(5-ethyl-2-thienylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 209

7-(2-furyl)-3-(3,4-methylenedioxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 210

3-(4-amino-3-ethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 211

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanone 212

N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)thiophene-2-carboxamide213

7-(2-furyl)-3-(6-hydroxymethyl-2- pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 214

N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)-3,3-dimethylbutanamide215

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)cyclopropanecarboxamide 216

7-(2-furyl)-3-(6-n-propyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 217

7-(2-furyl)-3-(6-isobutyloxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 218

3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 219

3-(4-amino-3-isopropylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 220

3-(6-cyanomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 221

3-(4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 222

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-nitrophenyl)ethanone 223

4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetyl)-benzonitrile 224

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamide 225

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-5-chloro-2- thiophenesulphonamide 226

7-(2-furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-aminehydrochloride 227

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-(N,N- diethylamino)phenyl)ethanone 228

7-(2-furyl)-3-(6-isopropyl-3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 229

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidin-3-yl)-1-(4-methoxyphenyl)ethanone 230

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-chloroindole-1-carboxylate 231

3-(5-chloro-7-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 232

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-3,5-dimethylisoxazol-4- ylsulphonamide 233

3-(6-(N,N-dimethylamino)methyl-2- pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 234

7-(2-furyl)-3-(6-methylthiomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 235

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(2-nitrophenyl)ethanone 236

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-1,2-dimethyl-1H-imidazol- 4-ylsulphonamide 237

N,N-bis(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-2-pyridylmethyl)methanesulphonamide 238

7-(2-furyl)-3-(6-methylsulphonylmethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 239

N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- pyridylmethyl)-N-methylmethanesulphonamide 240

3-(3-aminobenzyl)-7-(4,5-dimethyl-2- thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 241

3-(4-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 242

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-indanone 243

7-(2-furyl)-3-(5-methyl-7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 244

N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- methylphenyl)formamide245

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylpropanone 246

3-(7-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 247

7-(2-furyl)-3-(6-isopropoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 248

3-(6-ethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 249

3-(4-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 250

3-(7-bromo-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 251

3-(6-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 252

3-(3-(4-fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 253

3-(6-ethoxy-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 254

3-(6-ethoxy-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 255

3-(3-(2-pyridylmethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 256

7-(2-furyl)-3-(1-(4- frifluoromethylphenyl)ethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 257

3-(6-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 258

3-(5-fluoro-2-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 259

3-(3,5-dimethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 260

3-(1-(3-fluorophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 261

3-(7-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 262

3-(4-amino-3,5-dimethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 263

3-(1-(3-aminophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 264

7-(2-furyl)-3-(6-(2-methoxyethyl)-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 265

7-(2-furyl)-3-(1-(5,6-dimethyl-2-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5- d]pyrimidine-5-amine 266

3-(3-nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 267

7-(5-methyl-2-furyl)-3-(2-methyl-3- nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 268

7-(5-methyl-2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 269

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)phenyl)-N-methylcarbamate270

tert-butyl 2-(5-amino-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)pyrrole-1- carboxylate 271

7-(4,5-dimethylthiazol-2-yl)-3-(3- nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 272

3-(2-fluoro-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 273

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-methylindole-1-carboxylate 274

ethyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)- 2-methylphenyl)carbamate

The general synthetic methods used for the preparation of these Examplesare set out below as Methods A to BH. Table 2 sets out the Method usedfor each Example, together with analytical data.

HPLC is carried out using the following conditions: Column. WatersXterra RP 18 (50×4.6 mm); Particle size 5 μM; Mobile phase MeOH: 10 mMaq NH₄OAc (pH 7 buffer); Gradient 50:50 isocratic for 1 min. then lineargradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3 min.;Flow rate 2.0 mL/min.; Detection wavelength λ=230 nM. Retention timesare provided.

Method A 7-(2-Furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 1)

A solution of 7-chloro-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (570mg, 3.34 mmol) in N-methyl-2-pyrrolidinone (4 mL) was treated withPdCl₂(PPh₃)₂ (117 mg, 0.17 mmol) and 2-(tributylstannyl)furan (1.05 mL,1 mmol), stirred at 80° C. for 5 h, diluted with EtOAc, filtered througha silica pad and concentrated in vacuo. The residue was triturated withdiethyl ether and the title compound isolated as a yellow solid (438 mg,65%).

Method B3-(2-Fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 3)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(101 mg, 0.5 mmol) in DMF (2 mL), at 0° C., was treated with NaH (20 mg,60%, 0.5 mmol), stirred for 20 mins then treated with 2-fluorobenzylbromide (60 μL, 0.5 mmol). The reaction mixture was allowed to warm toroom temperature, stirred for 1 h, quenched with water, extracted withEtOAc, dried (MgSO₄) and concentrated in vacuo. The crude product waspurified by chromatography (EtOAc:Heptane, 1:4-EtOAc:Heptane, 2:1) togiveN,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 2) (28 mg, 11%) as a yellow solid and the title compound (34mg, 22%) as a yellow solid.

Method C3-(3-Aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 5)

A solution of7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(152 mg, 0.45 mmol) in EtOH (2 mL) at 50° C. was treated with a solutionof SnCl₂ (305 mg, 1.35 mmol) in conc. HCl (0.7 mL), stirred for 2 h,cooled, diluted with water, basified to pH 10 (5-M, NaOH) and filteredto give the title compound (127 mg, 92%) as a white solid.

Method DN-(3-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4-yl)sulphonamide(Example 9)

A solution of3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(125 mg, 0.41 mmol) in DMF (2 mL) was treated with Et₃N (85 μL, 0.61mmol) and 1-methylimidazole-4-sulphonyl chloride (74 mg, 0.41 mmol),stirred at room temperature overnight, poured into water, extracted withEtOAc, dried (MgSO₄) and concentrated in vacuo. The crude product waspurified by chromatography [SiO₂; EtOAc:MeOH (1:10)] to give the titlecompound (26 mg, 14%) as a cream solid.

Method E5-Amino-N-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide(Example 10)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(202 mg, 1.0 mmol) in DMF (3 mL) was treated with benzyl isocyanate (123μL, 1.0 mmol) and a catalytic amount of DMAP, stirred at roomtemperature overnight, diluted with EtOAc and filtered to give the titlecompound (62 mg, 19%) as a peach coloured solid.

Method F Ethyl5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate(Example 14)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(101 mg, 0.5 mmol) in DMF (4 mL) was treated with4-(N,N-dimethylamino)pyridine (5 mg, 0.04 mmol) and ethyl bromoacetate(55 μL, 0.5 mmol), stirred at room temperature for 16 h and purifieddirectly by chromatography [SiO₂; EtOAc:Heptane (1:2)] to give the titlecompound (50 mg, 35%) as a white solid.

Method G7-(2-Furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 18)

A solution of7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(119 mg, 0.37 mmol) in dichloromethane (20 mL) at 0° C. was treated withboron tribromide (1-M in dichloromethane, 8.8 mL, 8.8 mmol) portion-wiseover 3 days, concentrated in vacuo and isolated by filtration to givethe title compound (114 mg, 100%) as a yellow solid.

Method H 6-(5-Methyl-2-furyl)-5-nitropyrimidine-2,4-diamine

A solution of 6-chloro-5-nitropyrimidine-2,4-diamine (10 g, 60% pure, 32mmol) in THF (300 mL) was treated with saturated aq NaHCO₃ (75 mL),5-methylfuran-2-boronic acid (7.33 g, 0.058 mol) and Pd(PPh₃)₄ (1 g,0.865 mmol) and refluxed with vigorous stirring under argon overnight.The mixture was cooled to room temperature, diluted with EtOAc (400 mL)and water (300 mL), filtered to remove insoluble material and thefiltrate was extracted with EtOAc (2×100 mL). The combined organic phasewas dried (MgSO₄), concentrated in vacuo and the resulting solidtriturated with dichloromethane and filtered to give the title compound(6 g, 72%) as a yellow solid; mp 196.3-196.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3442, 3169, 2930, 1629, 1463, 1377, 1027, and 790; NMRδ_(H) (400 MHz, DMSO) 7.40 (2H, br s), 7.09 (2H, br s), 6.87 (1H, dd, J0.5, 3.2 Hz), 6.26 (2H, dd, J 1.0, 3.3 Hz) and 2.28 (3H, s).

Method I 6-(5-Methyl-2-furyl)pyrimidine-2,4,5-triamine

A suspension of 6-(5-methyl-2-furyl)-5-nitropyrimidine-2,4-diamine (6.6g, 29.6 mmol) and 10% Pd/C (0.66 g) in MeOH (100 mL) was heated at 40°C. under an atmosphere of H₂ for 3 h, cooled to room temperature,filtered through Celite, and concentrated in vacuo to give the titlecompound (5.8 g, 99%) as an off-white solid; IR ν_(max) (DR)/cm⁻¹ 3333,2237, 1634, 1458, 1237, 1025, 963 and 828; NMR δ_(H) (400 MHz, DMSO)6.77 (1H, dd, J 0.5, 3.2 Hz), 6.21-6.17 (3H, m), 5.14 (2H, s), 4.21 (2H,s), and 2.35 (3H, s).

Method J7-(5-Methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 19)

A solution of 6-(5-methyl-2-furyl)pyrimidine-2,4,5-triamine (5.8 g, 30.1mmol) in dioxane (116 mL) was treated with isoamyl nitrite (4.1 mL, 30.5mmol), heated at 80° C. for 3.5 h, cooled to room temperature and theresulting precipitate was filtered, washed with dioxane (10 mL) andheptane (2×15 mL) then triturated with heptane and filtered to give thetitle compound (4.7 g, 77%) as a sandy solid.

Method K 7-(1H-Pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 21)

A solution of7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.361 mmol) in MeOH (2 mL) was treated with HCl (4-M in dioxan,1 mL), stirred for 2 h, filtered and the resulting solid washed withEt₂O to give the title compound (76 mg, 100%) as a yellow solid.

Method L (2-Amino-6-(2-furyl)-5-nitropyrimidin-4-yl)4-methylbenzenesulphonate

A suspension of 2-amino-6-(2-furyl)-5-nitropyrimidine-4(1H)-one (1.00 g,4.50 mmol) in dichloromethane (50 mL) was treated with triethylamine(0.941 mL, 6.75 mmol) and p-toluenesulfonyl chloride (944 mg, 4.95mmol), stirred for 1 h, diluted with dichloromethane (50 mL), washedwith 2-M HCl (20 mL), dried (MgSO₄), concentrated in vacuo and purifiedby chromatography [SiO₂; isohexane:EtOAc (2:1)] to give the titlecompound (410 mg, 24%) as a yellow solid; NMR δ_(H) (400 MHz, CDCl₃)7.95 (2H, d, J 8.5 Hz), 7.59-7.57 (1H, m), 7.39 (2H, d, J 8.5 Hz),7.23-7.21 (1H, m), 6.59-6.51 (1H, m), 5.39 (2H, br s), 2.48 (3H, s);Retention time 5.68 min.

Method M 6-(2-Furyl)-5-nitro-N⁴-(2-pyridylmethyl)pyrimidine-2,4-diamine

A solution of (2-amino-6-(2-furyl)-5-nitropyrimidin-4-yl)4-methylbenzenesulphonate (478 mg, 1.27 mmol) in dimethoxyethane (15 mL)was treated with triethylamine (0.531 mL, 3.81 mmol) and2-pyridinemethylamine (0.393 mL, 3.81 mmol), stirred for 16 h, pouredinto water (100 mL) and the resulting solid was filtered to give thetitle compound (275 mg, 69%) as a yellow solid; NMR δ_(H) (400 MHz,CDCl₃) 8.70-8.58 (2H, m), 7.70-7.66 (1H, m), 7.55-7.54 (1H, m), 7.28(1H, d, J 8.0 Hz), 7.24-7.20 (1H, m), 7.07-7.06 (1H, m), 6.54-6.52 (1H,m), 5.26 (2H, br s) and 4.83 (2H, d, J 5.0 Hz); Retention time 1.44 min.

Method N7-(2-Furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 24)

A solution of6-(2-furyl)-5-nitro-N⁴-(2-pyridylmethyl)pyrimidine-2,4-diamine (270 mg,0.864 mmol) and 10% Pd/C (92 mg, 0.086 mmol) in EtOH (30 mL) and EtOAc(10 mL) was stirred under an hydrogen atmosphere for 1 h, filteredthrough Celite and concentrated in vacuo. The resulting yellow oil wasdissolved in dioxane (25 mL), treated with isoamyl nitrite (0.109 mL,0.815 mmol), stirred at 100° C. for 6 h, cooled to room temperature,filtered through Celite, concentrated in vacuo and triturated with Et₂Oto give the title compound (110 mg, 46%) as a yellow solid.

Method O(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid(Example 26)

A solution of ethyl5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate (547mg, 1.89 mmol) in MeOH (5 mL) was treated with aqueous NaOH (2 mL, 2-M,4 mmol), refluxed for 10 min, cooled, acidified with aqueous HCl (1-M),filtered and dried to give the title compound (417 mg, 85%) as a whitesolid.

Method P(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide(Example 31)

A suspension of(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid(140 mg, 0.5 mmol) in DMF (1 mL) was treated with carbonyl diimidazole(81 mg, 0.5 mmol), stirred at room temperature for 1 h, treated with3-chloroaniline (53 μL, 0.5 mmol) and the mixture heated to 50° C. for16 h. The reaction mixture was cooled, diluted with water (3 mL) andfiltered to give the title compound (94 mg, 48%) as a cream solid.

Method Q3-(2-Fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 34)

A stirred solution of thiazole (0.10 mL, 1.43 mmol) in dry THF (5 mL) at−78° C., under argon was treated with n-BuLi (0.9 mL, 1.6-M in hexanes,1.43 mmol), stirred for 30 min, treated with a solution of ZnCl₂ (1.8mL, 1-M in Et₂O, 1.80 mmol) and allowed to warm gradually to roomtemperature. The mixture was treated with7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.714 mmol) and Pd(PPh₃)₄ (50 mg), refluxed for 2 h andpartitioned between saturated NH₄Cl (20 mL) and EtOAc (20 mL). Theorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; iso-hexane:EtOAc (1:1)] to give the title compound(70 mg, 30%) as a cream solid.

Method RN-(2-Amino-6-(2-furyl)-5-nitropyrimidine-4-yl)-6-chloropyridine-3-carboxamide

A solution of 6-(2-furyl)-5-nitropyrimidine-2,4-diamine (500 mg, 2.26mmol) in pyridine (10 mL) was treated with 6-chloronicotinoyl chloride(438 mg, 2.49 mmol), stirred for 16 h at 80° C., cooled to roomtemperature, poured into water (100 mL) and extracted with EtOAc (2×25mL) and the combined organic phase was dried (MgSO₄), concentrated invacuo and purified by chromatography [SiO₂; isohexane:EtOAc (3:2)] togive the title compound (430 mg, 82%) as a yellow solid; NMR δ_(H) (400MHz, DMSO) 11.14 (1H, s), 8.86 (1H, d, J 2.5 Hz), 8.27 (1H, dd, J 8.5,2.5 Hz), 7.93 (1H, m), 7.77 (2H, br s), 7.65 (1H, d, J 7.5 Hz), 7.09(1H, d, J 4.5 Hz), 6.72-6.70 (1H, m); Retention time 2.41 min.

Method T6-Chloro-N-(7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-3-carboxamide(Example 44)

A solution ofN-(2-amino-6-(2-furyl)-5-nitropyrimidine-4-yl)-6-chloropyridine-3-carboxamide(153 mg, 0.423 mmol) and 10% Pd/C (82 mg, 42.3 μmol) in EtOH (20 mL) andEtOAc (5 mL) was stirred under an hydrogen atmosphere for 3 h, filteredthrough Celite and concentrated in vacuo to giveN-(2,5-diamino-6-(2-furyl)pyrimidin-4-yl)-6-chloropyridine-3-carboxamideas a yellow oil. A solution of this product in EtOH (5 mL) and 2-M HCl(5 mL) at 0° C. was treated dropwise with an ice-cold solution of sodiumnitrite (87 mg, 1.27 mmol) in water (2 mL). The mixture was stirred at0° C. for 1 h, stirred at room temperature for 1 h, neutralised with 5-MNaOH, stirred for 16 h and the resulting solid was filtered to givetitle compound (40 mg, 28%) as a brown solid.

Method U 6-Chloro-N⁴-(3-nitrobenzyl)pyrimidine-2,4,5-triamine

A mixture of 4,6-dichloropyrimidine-2,5-diamine (700 mg, 3.91 mmol),3-nitrobenzylamine hydrochloride (885 mg, 4.69 mmol) and triethylamine(1.6 mL, 11.7 mmol) in n-BuOH (20 mL) was refluxed for 17 h,concentrated in vacuo and the residue partitioned between EtOAc (10 mL)and H₂O (5 mL). The organic phase was dried (MgSO₄) and concentrated invacuo to give the title compound as an orange solid (906 mg, 76%) whichwas used in the next reaction without further purification; NMR δ_(H)(400 MHz, CDCl₃) 8.16 (1H, s), 8.10 (1H, d, J 8.0 Hz), 7.80 (1H, d, J7.5 Hz), 7.62 (1H, t, J 7.5 Hz), 7.25 (1H, t, J 6.0 Hz), 5.69 (2H, s),4.67 (2H, d, J 6.0 Hz) and 3.93 (2H, br s).

Method V 3-Chloromethyl-N,N-dimethylbenzamide

A solution of 3-(chloromethyl)benzoyl chloride (426 μL, 3 mmol) and Et₃N(626 μL, 4.5 mmol) in THF (5 mL) was treated with dimethylamine (1.5 mL,2-M in THF, 3 mmol), stirred at room temperature for 1 h, poured intowater, extracted with EtOAc, dried (MgSO₄) and concentrated in vacuo togive the title compound (580 mg, 98%) as a colourless oil; NMR δ_(H)(400 MHz, CDCl₃) 7.46-7.34 (4H, m), 4.59 (2H, s), 3.11 (3H, s) and 2.98(3H, s); Anal. Calcd for C₁₂H₁₂N₆O₂.0.2H₂O: C, 49.38; H, 4.28; N, 28.79.Found: C, 49.25; H, 4.09; N, 28.47.

Method W7-(2-Furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 66)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(606 mg, 3 mmol) in DMF (5 mL) at 0° C., was treated with CsCO₃ (977 mg,3 mmol), stirred for 1 h, treated with 2-methoxy-5-nitrobenzyl bromide(738 mg, 3 mmol) and stirred at room temperature for 1 h. The reactionmixture was diluted with water (10 mL), filtered and the resulting solidpurified by chromatography [SiO₂; EtOAc:Heptane (2:1)] to give the titlecompound (279 mg, 25%) as a yellow solid.

Method X3-(2-Fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 69)

A stirred solution of oxazole (138 mg, 2.0 mmol) in dry THF (10 mL) at−78° C., under argon was treated with n-BuLi (1.25 mL, 1.6-M in hexanes,2.0 mmol), stirred for 30 min, treated with a solution of ZnCl₂ (2.0 mL,1-M in Et₂O, 2.0 mmol)) and allowed to warm gradually to roomtemperature. The mixture was treated with7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(280 mg, 1.0 mmol) and Pd(PPh₃)₄ (100 mg), refluxed for 4 h andpartitioned between saturated NH₄Cl solution (10 mL) and EtOAc (10 mL).The organic phase was dried (MgSO₄), concentrated in vacuo and purifiedby chromatography [SiO₂; iso-hexane:EtOAc (1:1), then neat EtOAc] togive the title compound (6 mg, 2%) as a beige solid.

Method Y3-(2-Fluorobenzyl)-7-(1H-triazol-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 80)

A mixture of7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(145 mg, 0.50 mmol), tributyl1-(2-(trimethylsilyl)ethoxymethyl)-1H-triazol-5-ylstannane (336 mg, 0.75mmol) and Pd(PPh₃)₂Cl₂ (35 mg, 0.05 mmol) in DMF (2 mL) was shaken at80° C. for 17 h then purified directly by chromatography [SiO₂;iso-hexane:EtOAc (2:1)] to give3-(2-fluorobenzyl)-7-(1-(2-trimethylsilyl)ethoxymethyl)-1H-triazol-5-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineas a colourless oil. This material was dissolved in MeOH (1 mL), treatedwith a solution of HCl (0.5 mL, 4-M in dioxane), stirred for 17 h,concentrated in vacuo and the residue triturated with Et₂O to give thetitle compound (16 mg, 10%) as an off-white solid.

Method Z3-(4-Hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 87)

A solution of7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(60 mg, 0.17 mmol) in EtOH (40 mL), MeOH (20 mL) and water (15 mL) wastreated with ammonium chloride (280 mg, 5.23 mmol) and zinc (138 mg,2.05 mmol), stirred for 1 h, filtered through Celite, concentrated invacuo to ˜20 mL, diluted with brine (20 mL), extracted with EtOAc (3×20mL) and the combined organic phase dried (MgSO₄) and concentrated invacuo to give the title compound (40 mg, 73%) as a yellow solid.

Method AA3-(3-Aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(example 101)

A stirred solution of the7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(330 mg, 1 mmol) in dry DMF (5 mL) was treated with NaH (40 mg, 60% inoil, 1 mmol), stirred for 15 min, treated with tert-butylN-(3-(bromomethyl)benzyl)carbamate (300 mg, 1 mmol) and stirred for 1 h.The mixture was partitioned between EtOAc (20 mL) and H₂O (20 mL), theorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; iso-hexane:EtOAc (1:1)]. The resulting yellowsyrup was dissolved in MeOH (3 mL), treated with HCl (2 mL, 4-M indioxane), stirred for 17 h and the resulting solid filtered to give thetitle compound (258 mg, 80%) as a cream solid.

Method AB 2-Bromomethyl-6-(methoxymethyl)pyridine

A solution of 6-methoxymethyl-2-pyridinemethanol (860 mg, 5.64 mmol) andtriphenylphosphine (1.78 g, 6.77 mmol) in dichloromethane (40 mL) at 0°C. was treated portionwise with CBr₄ (2.80 g, 8.43 mmol), stirred for 1h, concentrated in vacuo and purified by chromatography [SiO₂;isohexane:EtOAc (3:1)] to give the title compound (1.20 g, 99%) as acolourless oil; NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 8.0 Hz), 7.35(2H, d, J 8.0 Hz), 4.58 (2H, s) and 4.54 (2H, s).

The following novel compounds were also synthesised by Method AB fromthe appropriate alcohol.

2-Bromomethyl-4-methylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 8.43 (1H, d, J 5.0 Hz), 7.26-7.25 (1H, m),7.03 (1H, d, J 5.0 Hz), 4.51 (2H, s) and 2.36 (3H, s).

2-Bromomethyl-6-ethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.60 (1H, t, J 7.5 Hz), 7.26 (1H, d, J 7.5Hz), 7.08 (1H, d, J 7.5 Hz), 4.53 (2H, s), 2.82 (2H, q, J 7.5 Hz) and1.30 (3H, t, J 7.5 Hz).

4-Bromomethyl-2-ethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 8.51 (1H, d, J 5.0 Hz), 7.17-7.16 (1H, m),7.13-7.11 (1H, m), 4.37 (2H, s), 2.84 (2H, q, J 7.5 Hz) and 1.32 (3H, t,J 7.5 Hz).

tert-Butyl (4-bromomethyl-3,5-difluorophenyl)carbonate

NMR δ_(H) (400 MHz, CDCl₃) 6.80 (2H, m), 4.49 (2H, s) and 1.56 (9H, s).

2-Fluoro-5-iodobenzyl bromide

NMR δ_(H) (400 MHz, DMSO) 7.94-7.91 (1H, dd, J 2.5, 7.5 Hz), 7.76-7.71(1H, m), 7.12-7.06 (1H, dd, J 8.5, 10.0 Hz) and 4.66-4.64 (2H, s).

2-Allyloxymethyl-6-bromomethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 7.5 Hz), 7.40 (1H, d, J 7.5Hz), 7.34 (1H, d, J 7.5 Hz), 6.03-5.93 (1H, m), 5.37-5.32 (1H, m),5.26-5.22 (1H, m), 4.64 (2H, s), 4.54 (2H, s) and 4.14-4.12 (2H, m).

4-Nitro-2-(2-trimethylsilylethoxy)methoxybenzyl bromide

NMR δ_(H) (400 MHz, CDCl₃) 7.99 (1H, d, J 2.0 Hz), 7.84 (1H, dd, J 8.4,2.0 Hz), 7.49 (1H, d, J 8.4 Hz), 5.41 (2H, s), 4.55 (2H, s), 3.82 (2H,m), 0.96 (2H, m) and 0.01 (9H, s).

2-Bromomethyl-4,6-diisopropylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.12 (1H, s), 6.93 (1H, s), 4.52 (2H, s),3.03 (1H, sept, J 7.0 Hz), 2.87 (1H, sept, J 7.0 Hz), 1.29 (6H, d, J 7.0Hz) and 1.25 (6H, d, J 7.0 Hz).

2-Bromomethyl-6-isopropylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.63-7.59 (1H, m), 7.27-7.25 (1H, m),7.10-7.08 (1H, m), 4.54 (2H, s), 3.06 (1H, sept, J 7.0 Hz) and 1.30 (6H,d, J 7.0 Hz).

2-Bromomethyl-6-vinylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.66 (1H, t, J 7.5 Hz), 7.34-7.28 (2H, m),6.81 (1H, dd, J 10.5, 17.5 Hz), 6.22 (1H, dd, J 1.0, 17.5 Hz), 5.51 (1H,dd, J 1.0, 10.5 Hz) and 4.55 (2H, s).

2-Bromomethyl-5-ethylthiophene

NMR δ_(H) (400 MHz, DMSO) 6.85-6.82 (1H, d, J 3.5 Hz), 6.71-6.68 (1H, d,J 3.5 Hz), 4.59-4.55 (2H, s), 2.81-2.75 (2H, m) and 1.25-1.20 (3H, m).

2-Bromomethyl-6-n-propylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.59 (1H, t, J 7.5 Hz), 7.26 (1H, d, J 7.5Hz), 7.06 (1H, d, J 7.5 Hz), 4.53 (2H, s), 2.76 (2H, t, J 7.5 Hz), 1.74(2H, sext, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).

2-Bromomethyl-6-isobutyloxymethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 7.5 Hz), 7.41 (1H, d, J 7.5Hz), 7.33 (1H, d, J 7.5 Hz), 4.62 (2H, s), 4.53 (2H, s), 3.33 (2H, d, J6.5 Hz), 1.91-2.01 (1H, m) and 0.96 (6H, d, J 6.5 Hz).

5-Bromomethyl-2-isopropylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 8.54 (1H, m), 7.65 (1H, dd, J 2.5, 8.0 Hz),7.16 (1H, d, J 8.0 Hz), 4.47 (2H, s), 3.07 (1H, sept, J 7.0 Hz) and 1.30(6H, d, J 7.0 Hz).

2-Bromomethyl-6-isopropyloxymethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.71-7.67 (1H, m), 7.42-7.40 (1H, m),7.33-7.31 (1H, m), 4.63 (2H, s), 4.53 (2H, s), 3.75 (1H, sept, J 6.0 Hz)and 1.25 (6H, d, J 6.0 Hz).

Method AC 2-Bromomethyl-4-nitropyridine

A solution of 2-methyl-4-nitropyridine (1.79 g, 13.0 mmol) in CCl₄ (30mL) was treated with N-bromosuccinimide (2.31 g, 13.0 mmol) and benzoylperoxide (420 mg, 1.30 mmol), stirred at 80° C. for 16 h, cooled to roomtemperature, filtered through Celite, concentrated in vacuo and purifiedby chromatography [SiO₂; isohexane:EtOAc (15:1)] to give the titlecompound (700 mg, 25%) as a colourless oil; NMR δ_(H) (400 MHz, CDCl₃)8.89 (1H, d, J 5.0 Hz), 8.19 (1H, d, J 2.0 Hz), 7.96 (1H, dd, J 5.0, 2.0Hz) and 4.66 (2H, s).

The following novel compounds were also synthesised by bromination ofthe appropriate arylalkyl compounds using Method AC.

2-Bromomethyl-6-methyl-4-nitropyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.99-7.98 (1H, m), 7.79 (1H, d, J 2.0 Hz),4.60 (2H, s) and 2.71 (3H, s).

tert-Butyl 7-bromomethylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.57 (1H, d, J 4.0 Hz), 7.55 (1H, dd, J 8.0,1.5 Hz), 7.27 (1H, d, J 7.5 Hz), 7.19 (1H, t, J 7.5 Hz), 6.58 (1H, d, J3.5 Hz), 5.24 (2H, s) and 1.68 (9H, s).

tert-Butyl 5-bromomethylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.11 (1H, br d, J 8.5 Hz), 6.72 (1H, d, J 3.5Hz), 7.59 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5, 1.5 Hz), 6.54 (1H, d,J 4.0 Hz), 4.64 (2H, s) and 1.67 (9H, s).

tert-Butyl 7-bromomethyl-5-chloroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, d, J 3.5 Hz), 7.51 (1H, d, J 2.0Hz), 7.27 (1H, m), 6.52 (1H, d, J 3.5 Hz), 5.15 (2H, s), and 1.67 (9H,s).

tert-Butyl 7-bromomethyl-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.53 (1H, d, J 4.0 Hz), 7.32 (1H, s), 7.09(1H, s), 6.49 (1H, d, J 3.5 Hz), 5.21 (2H, s), 2.41 (3H, s) and 1.66(9H, s).

tert-Butyl 5-bromomethyl-7-fluoroindole-1-carboxylate

NMR δ_(H) (CDCl₃) 7.65 (1H, d, J 4.0 Hz), 7.35 (1H, d, J 1.5 Hz), 7.07(1H, dd, J 13.0, 1.5 Hz), 6.56 (1H, dd, J 3.5, 1.5 Hz), 4.56 (2H, s) and1.65 (9H, s).

tert-Butyl 5-bromomethyl-4-chloroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.03 (1H, d, J 8.5 Hz), 7.63 (1H, d, J 4.0Hz), 7.36 (1H, d, 8.5 Hz), 6.71 (1H, d, J 3.5 Hz), 4.75 (2H, s) and 1.67(9H, s).

tert-Butyl 7-bromo-5-bromomethylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.57 (1H, s), 7.56-7.52 (2H, m), 6.54 (1H, d,J 3.5 Hz), 4.56 (2H, s) and 1.66 (9H, s).

tert-Butyl 5-bromomethyl-6-chloroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.23 (1H, br s), 7.60 (1H, s), 7.58 (1H, d, J3.5 Hz), 6.51 (1H, d, J 4.5 Hz), 4.71 (2H, s) and 1.67 (9H, s).

tert-Butyl 5-bromomethyl-6-fluoroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.88 (1H, br d, J 11.0 Hz), 7.57 (1H, d, J4.0 Hz), 7.54 (1H, d, J 7.0 Hz), 6.52 (1H, d, J 4.5 Hz), 4.64 (2H, s)and 1.67 (9H, s).

tert-Butyl 2-bromomethyl-5-fluoroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.12 (1H, dd, J 9.0, 4.5 Hz), 7.15 (1H, dd, J8.5, 2.5 Hz), 7.04 (1H, dt, J 9.0, 2.5 Hz), 6.66 (1H, s), 4.90 (2H, s)and 1.72 (9H, s).

tert-Butyl 5-bromomethyl-7-chloroindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.56 (1H, d, J 4.0 Hz), 7.49 (1H, d, J 2.0Hz), 7.37 (1H, s), 6.54 (1H, d, J 3.5 Hz), 4.56 (2H, s) and 1.65 (9H,s).

2-(1-Bromopropyl)-5,6-dimethylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.39 (1H, d, J 8.0 Hz), 7.18 (1H, d, J 8.0Hz), 4.93 (1H, t, J 7.5 Hz), 2.49 (3H, s), 2.27 (3H, s), 2.29-2.24 (2H,m) and 1.02 (3H, t, J 7.0 Hz); M/Z 228 (M+H)⁺.

The following novel compound was synthesised by bromination of2-(1-methoxypropyl)-6-methylpyridine using Method AC.

2-Bromo-1-(6-methylpyridin-2-yl)propanone

NMR δ_(H) (400 MHz, CDCl₃) 7.91 (1H, d, J 7.5 Hz), 7.74 (1H, t, J 7.5Hz), 7.35 (1H, d, J 7.5 Hz), 6.13 (1H, q, J 7.0 Hz), 2.62 (3H, s) and1.89 (3H, d, J 7.0 Hz).

Method AD) tert-Butyl 7-methylindole-1-carboxylate

A stirred solution of 7-methylindole (1.18 g, 9 mmol) in dry THF (50 mL)was treated with NaH (360 mg, 60% in oil, 9 mmol), stirred for 10 min,treated with di-tert-butyl dicarbonate (2.3 mL, 9.3 mmol), stirred for 1h, treated with 4-(N,N-dimethylamino)pyridine (catalytic amount) andstirred for 1 h. The mixture was partitioned between EtOAc (50 mL) andsaturated NH₄Cl solution (30 mL) and the organic phase was dried(MgSO₄), concentrated in vacuo, and purified by chromatography [SiO₂;iso-hexane:EtOAc (5:1)] to give the title compound (2.35 g, 100%) as anorange oil; NMR δ_(H) (400 MHz, CDCl₃) 7.51 (1H, d, J 4.0 Hz), 7.37 (1H,d, J 7.5 Hz), 7.13 (1H, t, J 7.5 Hz), 7.08 (1H, d, 7.5 Hz), 6.51 (1H, d,J 4.0 Hz), 2.64 (3H, s) and 1.63 (9H, s).

The following novel compounds were synthesised from the appropriateindoles using Method AD.

tert-Butyl 5-chloro-7-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.52 (1H, d, J 4.0 Hz), 7.35 (1H, d, J 2.0Hz), 7.07 (1H, d, J 1.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.61 (3H, s), and1.63 (9H, s).

tert-Butyl 5,7-dimethylindole-1-carboxylate

NMR δ_(H) (CDCl₃) 7.48 (1H, d, J 4.0 Hz) 7.16 (1H, s), 6.92 (1H, s),6.44 (1H, d, J 4.0 Hz), 2.60 (3H, s) 2.38 (3H, s) and 1.62 (9H, s).

tert-Butyl 7-fluoro-5-methylindole-1-carboxylate

NMR δ_(H) (CDCl₃) 7.59 (1H, d, J 4.0 Hz), 7.10 (1H, s), 6.84 (1H, d, J13.5 Hz), 6.50-6.47 (1H, m), 2.40 (3H, s) and 1.64 (9H, s).

tert-Butyl 4-chloro-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.92 (1H, d, J 8.0 Hz), 7.57 (1H, d, J 3.5Hz), 7.15 (1H, d, J 8.5 Hz), 6.66 (1H, d, J 3.5 Hz), 2.46 (3H, s) and1.66 (9H, s).

tert-Butyl 7-bromo-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.47 (1H, d, J 3.5 Hz), 7.35 (1H, s), 7.26(1H, s), 6.44 (1H, d, J 4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).

tert-Butyl 6-chloro-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.17 (1H, br s), 7.53 (1H, d, J 3.5 Hz), 7.38(1H, s), 6.46 (1H, d, J 3.0 Hz), 2.44 (3H, s), 1.67 (9H, s).

tert-Butyl 6-fluoro-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.79 (1H, br d, J 10.5 Hz), 7.51 (1H, d, J3.5 Hz), 7.30 (1H, d, J 7.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.34 (3H, s)and 1.66 (9H, s).

tert-Butyl 5-fluoro-2-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 8.04 (1H, dd, J 9.0, 4.5 Hz), 7.07 (1H, dd J9.0, 2.5 Hz), 6.92 (1H, dt, J 9.5, 3.0 Hz), 6.27 (1H, s), 2.58 (3H, d, J1.5 Hz) and 1.67 (9H, s).

tert-Butyl 7-chloro-5-methylindole-1-carboxylate

NMR δ_(H) (400 MHz, CDCl₃) 7.50 (1H, d, J 3.5 Hz), 7.22 (1H, s), 7.14(1H, s), 6.46 (1H, d, J 4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).

The following novel compound was synthesised from2,6-difluoro-4-hydroxybenzyl alcohol using Method AD.

tert-Butyl (3,5-difluoro-4-hydroxymethylphenyl)carbonate

IR ν_(max) (DR)/cm⁻¹ 3388, 2983, 1775, 1605, 1446, 1396, 1373, 1289,1146, 1072, 967 and 882; NMR δ_(H) (400 MHz, CDCl₃) 6.79 (2H, m), 4.75(2H, d, J 6.5 Hz), 1.84 (1H, t, J 6.5 Hz) and 1.56 (9H, s).

Method AE 2,6-Difluoro-4-hydroxybenzyl alcohol

A mixture of 3,5-difluorophenol (25 g, 0.19 mol) and KOH (85%, 12.7 g,0.19 mol) was treated dropwise with water (50 mL), stirred at 60° C. for1 h, treated dropwise with formaldehyde solution (37%, 15.6 mL, 0.19mol) and water (50 mL) and stirred overnight at 40° C. The mixture wascooled, acidified with 6-M HCl, filtered and the resulting solid washedwith water and dried to give the title compound (15 g, 49%) as a whitesolid: NMR δ_(H) (400 MHz, DMSO) 10.28 (1H, s), 6.43 (2H, m), 4.99 (1H,t, J 5.6 Hz) and 4.37 (2H, d, J 5.6 Hz).

Method AF7-(2-Furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 152)

A mixture of tert-butyl6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate(135 mg, 4.08 mmol), and NaOMe (22 mg, 4.08 mmol) in MeOH (10 mL) wasrefluxed for 1 h, treated with NaOMe (110 mg, 20.4 mmol), refluxed for afurther 4 h then stirred at room temperature for 17 h. The mixture wasconcentrated in vacuo to half volume and the resulting precipitate wasfiltered and washed with H₂O to give the title compound (90 mg, 96%) asa cream solid.

Method AG3-(2,6-Difluoro-4-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolol[4,5-d]pyrimidine-5-amine(Example 156)

A solution of3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride (130 mg, 0.34 mmol) in DMF (5 mL) at 0° C., was treatedwith CsCO₃ (223 mg, 0.68 mmol), stirred for 10 min, treated with methyliodide (21 μL, 0.34 mmol) and stirred at room temperature for 30 min.The reaction mixture was diluted with water (10 mL) and filtered to givethe title compound (122 mg, 100%) as a white solid.

Method AH 2-Fluoro-5-iodobenzyl alcohol

A solution of 2-fluoro-5-iodobenzaldehyde (1.173 g, 4.692 mmol) inisopropanol (25 mL) was treated with sodium borohydride (0.379 g, 10.02mmol), stirred at room temperature for 18 h, poured into water (125 mL),and extracted with isopropyl ether (2×25 mL). The combined organic phasewas dried (Na₂SO₄), and concentrated in vacuo to give the title compound(1.187 g, 99%) as a pale yellow solid; NMR δ_(H) (400 MHz, CDCl₃) 7.77(1H, m), 7.57 (1H, m), 6.82 (1H, t, J 8.8 Hz), 4.73 (2H, d, J 6.1 Hz),and 1.79 (1H, t, J 6.1 Hz).

Method AI 3-(tert-Butoxycarbonyloxy)-4-nitrobenzoic acid

A solution of 3-hydroxy-4-nitrobenzoic acid (1.83 g, 10 mmol) in THF (10mL) was treated with Et₃N (3.4 mL, 24 mmol) and di-tert-butyldicarbonate (2.40 mL, 11 μmol) and stirred at room temperature for 16 h.The reaction mixture was poured into 10% citric acid solution (20 mL),extracted with EtOAc (2×10 mL), dried (MgSO₄) and concentrated in vacuoto give the title compound (2.36 g, 83%) as a cream solid; IR ν_(max)(Nujol)/cm⁻¹ 2985, 1772, 1717 and 1592; NMR δ_(H) (400 MHz, DMSO) 13.85(1H, s), 8.26 (1H, d, J 8.5 Hz), 8.04 (1H, dd, J 8.5, 2.0 Hz), 7.98 (1H,d, J 2.0 Hz) and 1.49 (9H, s).

Method AJ tert-Butyl (5-bromomethyl-2-nitrophenyl)carbonate

A solution of 3-(tert-butoxycarbonyloxy)-4-nitrobenzoic acid (2.26 g, 8mmol) and N-methylmorpholine (1.85 mL, 16.8 mmol) in THF (20 mL) at 0°C., was treated with isobutylchloroformate (1.09 mL, 8.4 mmol) andstirred for 1 h. The reaction mixture was added to a cooled (−78° C.)solution of NaBH₄ (605 mg, 16 mmol) in MeOH (16 mL) and stirred at roomtemperature for 1 h. The reaction mixture was diluted with EtOAc (20mL), washed with saturated NaHCO₃ (10 mL) and 10% citric acid solution(10 mL), dried (MgSO₄) and concentrated in vacuo to give tert-butyl(5-hydroxymethyl-2-nitrophenyl)carbonate (1.36 g, 86%) as a cream solid.This material was brominated directly using Method AB to give the titlecompound (961 mg, 58%) as a yellow oil: NMR δ_(H) (400 MHz, CDCl₃) 8.09(1H, d, J 8.4 Hz), 7.41 (1H, dd, J 8.4, 2.0 Hz), 7.34 (1H, d, J 2.0 Hz),4.47 (2H, s) and 1.58 (9H, s).

Method AK3-(3-Nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride (Example 266)

A solution of7-chloro-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(306 mg, 1 mmol),1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-ylboronic acid (2 mmol),Pd(PPh₃)₄ (100 mg) and saturated NaHCO₃ (5 mL) in THF (20 mL) wasrefluxed for 2 h, diluted with water (20 mL), extracted with EtOAc (2×20mL), dried (MgSO₄), concentrated in vacuo and purified by chromatography[SiO₂; CH₂Cl₂:EtOAc (6:1)] to give3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(156 mg, 34%) as a pale yellow syrup.

A solution of3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(156 mg, 0.34 mmol) in MeOH (2 mL) was treated with 4-M HCl in dioxane(4 mL) stirred at room temperature for 2 h, concentrated in vacuo,triturated with Et₂O and filtered to give the title compound (110 mg,97%) as a yellow solid.

Method AL3-(6-Acetamidomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 177)

A suspension of7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(210 mg, 0.465 mmol) in EtOH (50 mL) was treated with ethylenediamine(62 μl, 0.929 mmol), stirred for 3 h at 90° C. and the resulting clearsolution, cooled to room temperature and concentrated in vacuo to give3-(6-aminomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine.A solution of this material in pyridine (10 mL) at 0° C. was treatedwith acetyl chloride (109 ml, 1.53 mmol), stirred for 10 min, pouredinto water (70 mL), extracted with EtOAc (3×20 mL) and the combinedorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; EtOAc] to give the title compound (110 mg, 65%) asa beige solid.

Method AM3-(6-Allyloxymethyl-2-pyridylmethyl)-N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 182)

A solution of7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.377 mmol) in DMF (5 mL) at 0° C. was treated with sodiumhydride (30 mg, 0.743 mmol), stirred for 15 min, treated with allylbromide (96 μl, 1.11 mmol), stirred at room temperature for 16 h,concentrated in vacuo to ˜2 mL and purified by chromatography [SiO₂;isohexane:EtOAc (3:1)] to give the title compound (50 mg, 30%) as ayellow solid.

Method AN 6-Allyloxymethyl-2-pyridinemethanol

A solution of 2,6-pyridinedimethanol (5.0 g, 35.9 mmol) in DMF (30 mL)at 0° C. was treated with sodium hydride (1.44 g, 35.9 mmol), stirredfor 30 min, treated with allyl bromide (3.42 ml, 39.5 mmol), stirred for16 h at room temperature, poured into water (150 mL), extracted withEtOAc (3×30 mL) and the combined organic phase was dried (MgSO₄),concentrated in vacuo and purified by chromatography [SiO₂;isohexane:EtOAc (3:1 to 1:1)] to give the title compound (1.56 g, 24%)as a colourless oil: NMR δ_(H) (400 MHz, CDCl₃) 7.69 (1H, t, J 7.5 Hz),7.37 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 6.04-5.93 (1H, m),5.38-5.21 (2H, m), 4.74 (2H, d, J 5.0 Hz), 4.65 (2H, s), 4.15-4.09 (2H,m) and 3.76 (1H, t, J 5.0 Hz).

The following novel compounds were synthesised from the appropriatealcohols by Method AN

2-(1-Methoxypropyl)-6-methylpyridine

NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, t, J 8.0 Hz), 7.18 (1H, d, J 8.0Hz), 7.04 (1H, d, J 8.0 Hz), 4.17 (1H, dd, J 5.5, 7.5 Hz), 3.30 (3H, s),2.55 (3H, s), 1.84-1.69 (2H, m) and 0.93 (3H, t, J 7.5 Hz).

6-Isobutyloxymethylpyridine-2-methanol

NMR δ_(H) (400 MHz, CDCl₃) 7.69 (1H, t, J 7.5 Hz), 7.37 (1H, d, J 7.5Hz), 7.13 (1H, d, J 7.5 Hz), 4.74 (2H, s), 4.63 (2H, s), 3.94 (1H, brs), 3.33 (2H, d, J 6.5 Hz), 1.91-2.01 (1H, m) and 0.96 (6H, d, J 6.5Hz).

6-Isopropyloxymethylpyridine-2-methanol

NMR δ_(H) (400 MHz, CDCl₃) 7.70-7.66 (1H, m), 7.39 (1H, d, J 7.5 Hz),7.11 (1H, d, J 8.0 Hz), 4.74 (2H, s), 4.64 (2H, s), 3.75 (1H, sept, J6.0 Hz) and 1.25 (6H, d, J 6.0 Hz).

Method AO 3-Isopropyl-4-nitrobenzyl bromide

A solution of 4-nitrobenzyl bromide (432 mg, 2 mmol) in THF (5 mL) at−70° C., was treated dropwise with isopropylmagnesium chloride (1 mL,2-M in Et₂O, 2 mmol), stirred for 1 h, treated with DDQ (499 mg, 2.2mmol) and stirred at room temperature for 16 h. The reaction mixture waspoured into water (10 mL), extracted with EtOAc (2×10 mL), dried(MgSO₄), concentrated in vacuo and filtered. The resulting solid waspurified by chromatography [SiO₂; EtOAc:Heptane (1:4)] to give the titlecompound (183 mg, 35%) as a pale yellow solid which was used in the nextreaction without further purification.

The following novel compound was also synthesised from 4-nitrobenzylbromide using Method AO

3-Ethyl-4-nitrobenzyl bromide

NMR δ_(H) (400 MHz, CDCl₃) 7.87 (1H, d, J 8.3 Hz), 7.37 (1H, s), 7.35(1H, d, J 8.3 Hz), 4.47 (2H, s), 2.92 (2H, q, J 7.5 Hz) and 1.30 (3H, t,J 7.5 Hz).

Method AP 2-(Trimethylsilyl)ethoxymethyl4-nitro-2-((2-trimethylsilyl)ethoxymethoxy)benzoic acid

A solution of 2-hydroxy-4-nitrobenzoic acid (1.83 g, 10 mmol) in THF (20mL), was treated with N,N-diisopropylethylamine (3.92 mL, 22 mmol) and2-(trimethylsilyl)ethoxymethyl chloride (3.46 mL, 20 mmol) and stirredfor 16 h then purified directly by chromatography [SiO₂: EtOAc:heptane(1:4)] to give the title compound (5.82 mg, quantitative) as white solidwhich was used in the next reaction without further purification; NMRδ_(H) (400 MHz, CDCl₃) 8.09-8.07 (1H, m), 7.87-7.85 (2H, m), 5.50 (2H,s), 5.35 (2H, s), 3.78 (4H, t, J 8.5 Hz), 1.00-0.88 (4H, m), 0.00 (9H,s) and 0.03 (9H, s).

Method AQ 2-(2-Trimethylsilyl)ethoxymethoxy-4-nitrobenzyl alcohol

A solution of 2-(trimethylsilyl)ethoxymethyl4-nitro-2-(2-(trimethylsilyl)ethoxymethoxy)benzoic acid (2.91 mg, 5mmol) in Et₂O (10 mL) at 0° C., was treated with LiAlH₄ (190 mg, 22mmol) and stirred for 30 min. The reaction mixture was poured into water(20 mL), extracted with EtOAc (2×10 mL), dried (MgSO₄) and concentratedin vacuo to give the title compound (1.35 g, 91%) as a slightly impurecolourless oil; NMR δ_(H) (400 MHz, CDCl₃) 7.96-7.99 (1H, m), 7.90 (1H,dd, J 8.5, 2.0 Hz), 7.55 (1H, d, J 8.5 Hz), 5.35 (2H, s), 4.78 (2H, s),3.80-3.74 (2H, m), 0.99-0.94 (2H, m) and 0.00 (9H, s).

Method AR 4,6-Diisopropyl-2-pyridinemethanol

A solution of 2-pyridinemethanol (5.00 g, 45.8 mmol), conc. sulfuricacid (2.44 ml, 45.8 mmol), iron(II) sulfate heptahydrate (1.53 g, 5.50mmol) and isopropyl iodide (13.7 ml, 137 mmol) in DMSO (150 mL) wastreated dropwise with hydrogen peroxide (27.5 wt % in H₂O, 17.0 mL, 137mmol), with ice-bath cooling to maintain the internal temperature at25-30° C. A further portion of iron(II) sulfate heptahydrate (1.53 g,5.50 mmol) was added, the mixture was allowed to cool to roomtemperature over 1 h, poured into water (500 mL), basified to pH 9 with5-M NaOH, extracted with dichloromethane (3×100 mL) and the combinedorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; isohexane:EtOAc (3:2)] to give4,6-diisopropyl-2-pyridinemethanol (500 mg, 6%) as a colourless oil; NMRδ_(H) (400 MHz, CDCl₃) 6.90 (1H, s), 6.85 (1H, s), 4.69 (2H, br s), 4.35(1H, br s), 3.03 (1H, sept, J 7.0 Hz), 2.87 (1H, sept, J 7.0 Hz), 1.30(6H, d, J 7.0 Hz) and 1.25 (6H, d, J 7.0 Hz), and6-isopropyl-2-pyridinemethanol (900 mg, 13%) as a colourless oil.

The following novel compound was also synthesised from2-pyridinemethanol by Method AR.

6-n-Propyl-2-pyridinemethanol

NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, t, J 7.5 Hz), 7.03 (2H, t, J 7.5Hz), 4.72 (2H, s), 4.15 (1H, br s), 2.77 (2H, t, J 7.5 Hz), 1.77 (2H,sept, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).

Method AS tert-Butyl5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate(Example 203)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(300 mg, 1.49 mmol) in DMF (5 mL), at 0° C., was treated with 60% sodiumhydride in mineral oil (60 mg, 1.49 mmol), stirred for 30 minutes,treated with tert-butyl 4-(bromomethyl)phenylcarbonate (471 mg, 1.64mmol), stirred at room temperature for 16 h, and purified bychromatography [SiO₂; EtOAc: heptane, (1:2)] to give the title compound(55 mg, 12%) as a beige solid.

Method AT2-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanone(Example 211)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(101 mg, 0.5 mmol) in DMF (2 mL) was treated with 2-bromoacetophenone(100 mg, 0.5 mmol) and triethylamine (105 μL, 0.75 mmol), stirred atroom temperature for 3 days, diluted with water (100 mL) and filtered.The resulting solid was purified by chromatography [SiO₂; Hexane: EtOAc,(3:1 to 1:1)] to give the title compound (20 mg, 13%) as a yellow solid.

Method AU7-(2-Furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride (Example 213)

A solution of6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2-carboxaldehyde(62 mg, 0.193 mmol) in MeOH (20 mL) was treated with acetic acid (5 mL),dimethylamine (2-M in MeOH, 1.93 mL, 3.86 mmol) and sodiumcyanoborohydride (242 mg, 3.86 mmol), stirred for 16 h and concentratedin vacuo. The residue was treated with saturated NaHCO₃ solution (20mL), extracted with EtOAc (3×10 mL) and the combined organic phase dried(MgSO₄), concentrated in vacuo and purified by chromatography [SiO₂;EtOAc] to give the free base as a yellow solid. The solid was suspendedin MeOH (1 mL), treated with HCl (4-M in dioxane, 0.25 mL), stirred for10 min, concentrated in vacuo and triturated with Et₂O to give the titlecompound (22 mg, 29%) as a yellow solid.

Method AV3-(6-Cyanomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 220)

A solution of3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.517 mmol) and sodium cyanide (51 mg, 1.03 mmol) in DMF (5 mL)was stirred at 60° C. for 16 h, poured into water (40 mL), extractedwith EtOAc (3×8 mL), the combined organic phase dried (MgSO₄),concentrated in vacuo and purified by chromatography[SiO₂;isohexane:EtOAc (1:1)] to give title compound (50 mg, 26%) as ayellow solid.

Method AW3-(4-Hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 221)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(400 mg, 1.98 mmol) in DMF (3 mL), at 0° C., was treated with 60% sodiumhydride in mineral oil (80 mg, 1.98 mmol), stirred for 30 min, treatedwith 4-(2-(trimethylsilyl)ethoxymethoxy)benzyl bromide (1.23 g, 3.96mmol), stirred at room temperature for 48 h and purified bychromatography [SiO₂; EtOAc: heptane, (1:2)]. The resulting yellow solidwas dissolved in MeOH:DMF (1:2), passed through an ion exchangecartridge (Isolute SPE SCX-2), concentrated in vacuo, and washed withwater and ether to give the title compound (41 mg, 7%) as a pale yellowsolid.

Method AXN-(3-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamide(Example 224)

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(153 mg, 0.5 mmol) in pyridine (2 mL) at 0° C. was treated withpropanesulfonyl chloride (62 μL, 0.55 mmol) and shaken at roomtemperature for 16 h. The mixture was poured into water (50 mL),extracted with EtOAc (2×10 mL), washed with 10% citric acid (10 mL) andthe combined organic phase dried (MgSO₄) and concentrated in vacuo togive the title compound (111 mg, 54%) as a cream solid.

Method AY7-(2-Furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 226)

A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55 mmol) inDMF (5 mL) at 0° C. was treated with sodium hydride (60% dispersion inmineral oil; 62 mg, 1.55 mmol), stirred for 15 min, treated with3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.310 mmol), stirred at 50° C. for 1 h, cooled to roomtemperature, poured into water (20 mL), extracted with EtOAc (3×10 mL)and the combined organic phase dried (MgSO₄) and concentrated in vacuoto giveN-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide.A solution of this product in MeOH (20 mL) was treated with a solutionof sodium (71 mg, 3.10 mmol) in MeOH (10 mL), stirred for 16 h,concentrated in vacuo, treated with EtOAc (20 mL), filtered throughCelite and concentrated in vacuo. The resulting solid was suspended inMeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10min, concentrated in vacuo and triturated with Et₂O to give the titlecompound (80 mg, 58%) as a yellow solid.

Method AZ3-(1H-Benzotriazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 158)

A mixture of 5-methyl-1H-benzotriazole (666 mg, 5 mmol) in THF (20 mL)was treated with NaH (60% dispersion, 200 mg, 5 mmol), stirred at roomtemperature for 10 min, treated with di-tert-butyl dicarbonate (115 mg,5 mmol) and stirred overnight. The mixture was treated with saturatedNaHCO₃ solution (10 mL), extracted with EtOAc (2×10 mL), dried (MgSO₄),filtered through a plug of SiO₂ and concentrated in vacuo to givetert-butyl 5-methylbenzotriazole-1-carboxylate (as a mixture with the6-methyl regioisomer) (1.08 g, 92%) as a colourless oil.

A solution of tert-butyl 5-methyl-1H-benzotriazole-1-carboxylate (as amixture with the 6-methyl regioisomer) (1.08 g, 4.63 mmol), benzoylperoxide (112 mg, 0.46 mmol) and N-bromosuccinnimide (0.76 g, 4.63 mmol)in CCl₄ (25 mL) was refluxed overnight, cooled, filtered, concentratedin vacuo and purified by chromatography [SiO₂; isohexane:EtOAc (10:1)]to give tert-butyl 5-(bromomethyl)-1H-benzotriazole-1-carboxylate (666mg, 46%) (as a mixture with the 6-bromomethyl regioisomer) as acolourless oil.

A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(404 mg, 2 mmol) in DMF (4 mL) was treated with NaH (60% dispersion, 80mg, 2 mmol), stirred at room temperature for 10 min, treated with asolution of tert-butyl 5-(bromomethyl)-1H-benzotriazole-1-carboxylate(as a mixture with the 6-bromomethyl regioisomer) (624 mg, 2 mmol) inDMF (2 mL) and stirred overnight. The mixture was concentrated in vacuoand purified by chromatography [SiO₂, isohexane:EtOAc (2:1)] to givetert-butyl5-(5-amino-7-(2-furyl)-3H-triazolo[4,5-d]pyrimidin-3-yl)methyl-1H-benzotriazol-1-carboxylate(135 mg, 24%) (as a mixture with the 6-substituted regioisomer) as awhite solid.

A solution of tert-butyl5-(5-amino-7-(2-furyl)-3H-triazolo[4,5-d]pyrimidin-3-yl)methyl-1H-benzotriazol-1-carboxylate(as a mixture with the 6-substituted regioisomer) (135 mg, 0.31 mmol) inMeOH (5 mL) and THF (5 mL) was treated with 40% aqueous dimethylamine(0.176 mL, 1.56 mmol), refluxed for 25 min, concentrated in vacuo andthe resulting solid triturated with ether, filtered, triturated withMeOH, filtered and dried to give the title compound (31 mg, 30%) as ayellow solid.

Method BA Ethyl4-((5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl)methyl)-2-methylphenylcarbamate(Example 274)

A suspension of3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(260 mg, 0.812 mmol) in pyridine (5 mL) at room temperature was treateddropwise with ethyl chloroformate (0.155 mL, 1.62 mmol), stirred for 30min, poured into water (30 mL), extracted with EtOAc (2×10 mL) and thecombined organic phase was dried (MgSO₄) and concentrated in vacuo togive the title compound (318 mg, 100%) as a beige solid.

Method BBN-(4-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-methylphenyl)formamide(Example 244)

A mixture of ethyl4-((5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl)methyl)-2-methylphenylcarbamate(318 mg, 0.81 mmol) and LiAlH₄ (62 mg, 1.62 mmol) in dry THF (30 mL) wasrefluxed overnight, cooled to room temperature, treated with 13% aqueousNaOH solution (0.1 mL) then water (0.3 mL), stirred for 30 min, filteredthrough Celite and concentrated in vacuo. The resulting solid wastriturated with THF and filtered to give the title compound (20 mg, 7%)as a yellow solid.

Method BC 7-Fluoro-5-methylindole

A solution of chloral hydrate (7.3 g, 44 mmol), sodium sulphatedecahydrate (52 g, 160 mmol) and H₂O (100 mL) was added slowly to astirred solution of 2-fluoro-4-methylaniline (5.0 g, 40 mmol),hydroxylamine hydrochloride (11.1 g, 160 mmol) and conc. HCl (3 mL) inH₂O (50 mL). The reaction mixture was refluxed for 1 h, stirred at roomtemperature for 5 h, filtered and the resulting solid crystallised fromMeOH/H₂O to yield brown crystals (1.53 g). This material was added insmall portions with stirring to conc. sulphuric acid (20 mL) at 70° C.,stirred for 1 h, then added slowly with rapid stirring to ice/H₂O (200mL), extracted twice with EtOAc (2×25 mL) and the combined organic phasedried (MgSO₄) and concentrated in vacuo to give 7-fluoro-5-methylisatin(1.68 g, 24%) as a dark red gum.

A solution of 7-fluoro-5-methylisatin (1.68 g, 9.43 mmol) in dry THF (50mL) was added slowly to an ice cold, stirred suspension of LiAlH₄ (1.18g, 31 mmol) in dry THF (50 mL), refluxed for 2 h, cooled to roomtemperature then treated sequentially with H₂O (1.2 mL), 15% NaOH (1.2mL) and H₂O (3 mL). The solution was filtered through a pad of Celite,washing the filter cake thoroughly with THF, the deep blue filtrate wasconcentrated in vacuo and purified by chromatography [SiO₂;iso-Hexane:EtOAc (9:1)] to give the title compound (480 mg, 41%) as apale blue oil; NMR δ_(H) (CDCl₃) 8.19 (1H, br s), 7.21-7.16 (2H, m),6.74 (1H, d, J 12.0 Hz), 6.51-6.46 (1H, m) and 2.42 (3H, s).

Method BE3-(7-Fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 246)

A stirred suspension of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (303 mg, 1.5mmol) in DMF (2 mL) was treated with NaH (60% dispersion in oil, 60 mg,1.5 mmol), stirred for 10 min, treated slowly with a solution oftert-butyl 5-bromomethyl-7-fluoroindole-1-carboxylate (460 mg, 1.5 mmol)in DMF (1 mL), stirred for 2 h then the mixture was purified directly bychromatography [SiO₂; iso-hexane:EtOAc (2:1)] to give the BOC protectedproduct (180 mg, 0.417 mmol) as a pale green solid. This material wasdissolved in MeOH (5 mL), treated with sodium methoxide (113 mg, 2mmol), refluxed for 4 h, cooled to room temperature, diluted with H₂Oand filtered to give the title compound (118 mg, 81%) as a cream solid.

Method BF3-(3-(4-Fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 252)

A suspension of3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.65 mmol) and 4A molecular sieves in THF (10 mL) was treatedwith 4-fluorobenzaldehyde (0.04 mL, 0.37 mmol), heated to 40° C. for 3h, cooled to room temperature, treated sodium triacetoxyborohydride (400mg, 1.89 mmol) and acetic acid (0.1 mL) and stirred for 15 minutes. Thereaction was quenched by addition of sat. NaHCO₃ (5 mL), extracted withEtOAc (2×5 mL) and the combined organic phase dried (MgSO₄),concentrated in vacuo and purified by chromatography [(SiO₂;EtOAc:Heptane (1:2)] to give the title compound (60 mg, 44%) as a whitesolid.

Method BG 2-(2-Methoxyethyl)-6-(triphenylmethoxy)methylpyridine

A stirred solution of (methoxymethyl)triphenylphosphonium chloride (2.79g, 8.13 mmol) in THF (50 mL) at 0° C. was treated dropwise with n-BuLi(1.6-M in hexanes, 5.08 mL, 8.13 mmol), stirred for 1 h, treated with asolution of 6-(triphenylmethoxy)methylpyridine-2-carboxaldehyde (1.54 g,4.06 mmol) in THF (15 mL) and allowed to warm to room temperatureovernight. The reaction was treated with saturated NH₄Cl solution (5mL), diluted with water (50 mL), extracted with EtOAc (2×50 mL) and thecombined organic phase diluted with iso-hexane (50 mL), dried (MgSO₄),filtered through silica and concentrated in vacuo to give2-(2-methoxyethenyl)-6-(triphenylmethoxy)methylpyridine (1.58 g) as ayellow oil. A solution of this crude alkene and 10% Pd/C (216 mg, 0.203mmol) in EtOAc (50 mL) was stirred under a hydrogen atmosphere for 16 h,filtered through Celite and concentrated in vacuo to give the titlecompound (1.08 g, 65%) as a yellow oil; NMR δ_(H) (400 MHz, CDCl₃)7.67-7.64 (1H, m), 7.52-7.49 (6H, m), 7.32-7.21 (10H, m), 7.09-7.07 (1H,m), 4.34 (2H, s), 3.69 (2H, t, J 6.5 Hz), 3.32 (3H, s) and 2.98 (2H, t,J 6.5 Hz); M/Z 410 (M+H)⁺.

Method BH 2-Bromomethyl-6-(2-methoxyethyl)pyridine

A solution of 2-(2-methoxyethyl)-6-(triphenylmethoxy)methylpyridine(1.08 g, 2.64 mmol) in 4-M HCl in dioxan (10 mL, 40.0 mmol) was stirredfor 4 h and concentrated in vacuo. The residue was partitioned betweendichloromethane (15 mL) and saturated NaHCO₃ solution (15 mL), theaqueous phase was extracted with dichloromethane (10 mL) and thecombined organic phase was dried (MgSO₄) and concentrated in vacuo togive 6-(2-methoxyethyl)pyridine-2-methanol. A solution of this productin dichloromethane (40 mL) at 0° C. was treated with triphenylphosphine(830 mg, 3.16 mmol) followed portionwise by carbon tetrabromide (1.31 g,3.96 mmol), stirred for 1 h, concentrated in vacuo and purified bychromatography [SiO₂; isohexane:EtOAc (4:1)] to give the title compound(303 mg, 50%) as a yellow oil; NMR δ_(H) (400 MHz, CDCl₃) 7.60 (1H, t, J7.5 Hz), 7.28 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 4.53 (2H, s),3.76 (2H, t, J 6.5 Hz), 3.35 (3H, s) and 3.05 (2H, t, J 6.5 Hz).

Experimental data for Examples 1-274 are provided in Table 2.

HPLC is carried out using the following conditions: Column. WatersXterra RP 18 (50×4.6 mm); Particle size 5 μM; Mobile phase MeOH: 10 mMaq NH₄OAc (pH 7 buffer); Gradient 50:50 isocratic for 1 min. then lineargradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3 min.;Flow rate 2.0 mL/min.; Detection wavelength λ=230 nM. Retention timesare provided in Table 2.

TABLE 2 Example Method Yield (%) Physical Data 1 A 65 IR ν_(max)(Nujol)/cm⁻¹ 3403, 3329, 3134, 2925, 1656, 1634, 1582, 1565, 1463 and1377; NMR δ_(H) (400 MHz, DMSO) 6.83-6.87 (1H, m), 7.12 (2H, s), 7.89(1H, d, J 3.1 Hz), 8.09-8.10 (1H, m), 15.52 (1H, s); M/Z 203 (M + H)⁺. 2B 11 IR ν_(max) (Nujol)/cm⁻¹ 2924, 2854, 1612, 1587, 1526, 1489, 1456,1372, 1221 and 753; NMR δ_(H) (400 MHz, DMSO) 4.98 (2H, s), 5.14 (2H,s), 5.71 (2H, s), 6.85-6.87 (1H, m), 7.00-7.14 (3H, m), 7.14-7.46 (9H,m), 7.89 (1H, d, J 3.5 Hz), 8.16 (1H, d < J 1.0 Hz); Anal. Calcd forC₂₉H₂₁F₃N₆O•0.25H₂O: C, 65.59; H, 4.08; N, 15.83. Found: C, 65.46; H,4.03; N, 15.76. 3 B 22 IR ν_(max) (Nujol)/cm⁻¹ 3480, 3312, 3195, 3118,2925, 2854, 1652, 1609, 1581, 1487, 1456, 1436, 1027 and 759; NMR δ_(H)(400 MHz, DMSO) 5.60 (2H, s), 6.84-6.86 (1H, m), 7.15-7.29 (3H, m),7.32-7.43 (3H, m), 7.89 (1H, d, J 2.9 Hz), 8.12 (1H, s). 4 B 9 mp221.0-221.1° C.; IR ν_(max) (Nujol)/cm⁻¹ 3470, 3310, 3191, 3144, 2924,2854, 1642, 1610, 1521, 1463 and 1354; NMR δ_(H) (400 MHz, DMSO) 5.85(2H, s), 6.87 (1H, s), 7.37 (2H, s), 7.63-7.73 (2H, m), 7.91 (1H, d, J2.8 Hz), 8.13 (1H, s), 8.18 (1H, s), 8.20 (1H, s). Anal. Calcd forC₁₅H₁₁N₇O₃: C, 50.57; H, 3.11; N, 27.52. Found: C, 50.99; H, 3.23; N,27.21. 5 C 92 mp 259.8-259.9° C.; IR ν_(max) (Nujol)/cm⁻¹ 3452, 3367,3318, 3185, 3142, 2922, 1651, 1602, 1514, 1463 and 1377; NMR δ_(H) (400MHz, DMSO) 5.09 (2H, s), 5.49 (2H, s), 6.35 (1H, s), 6.41 (1H, d, J 7.5Hz), 6.45 (1H, d, J 8.0 Hz), 6.85-6.86 (1H, m), 6.96 (1H, t, J 8.0 Hz),7.30 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11 (1H, s). Anal. Calcd forC₁₅H₁₃N₇O: C, 56.63; H, 4.50; N, 30.82. Found: C, 56.82; H, 4.25; N,30.57. 6 B 21 IR ν_(max) (Nujol)/cm⁻¹ 3405, 3328, 3211, 3155, 2925,2854, 1719, 1603, 1577, 1463, 1023 and 731; NMR δ_(H) (400 MHz, DMSO)3.84 (3H, s), 5.76 (2H, s), 6.85-6.87 (1H, m), 7.33-7.38 (2H, s),7.50-7.59 (2H, m), 7.89-7.92 (3H, s), 8.12-8.13 (1H, m); Anal. Calcd forC₁₇H₁₄N₆O₃•0.25H₂O: C, 57.54; H, 4.12; N, 23.68. Found: C, 57.42; H,3.75; N, 23.37. 7 B 27 IR ν_(max) (Nujol)/cm⁻¹ 3506, 3309, 3189, 3131,2925, 2854, 1635, 1606, 1580, 1502, 1417, 1204, 1025 and 762; NMR δ_(H)(400 MHz, DMSO) 3.70 (6H, s), 5.58 (2H, s), 6.44 (3H, s), 6.84-6.87 (1H,m), 7.34 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11-8.12 (1H, m); Anal. Calcdfor C₁₇H₂₁₆N₆O₃•0.5H₂O: C, 56.50; H, 4.74; N, 23.26. Found: C, 56.44; H,4.56; N, 22.98. 8 B 21 IR ν_(max) (Nujol)/cm⁻¹ 3488, 3314, 3146, 2922,2853, 1667, 1608, 1583, 1463 and 1378; NMR δ_(H) (400 MHz, DMSO) 5.79(2H, s), 6.84-6.87 (1H, m), 7.01 (1H, d, J 4.0 Hz), 7.05 (1H, d, J 4.0Hz), 7.38 (2H, s), 7.89 (1H, d, J 3.5 Hz), 8.11-8.13 (1H, m). 9 D 14 IRν_(max) (Nujol)/cm⁻¹ 3458, 3299, 3174, 3111, 2923, 1625, 1605, 1463 and1377; NMR δ_(H) (400 MHz, DMSO) 3.61 (3H, s), 5.58 (2H, s), 6.84-6.94(3H, m), 7.06-7.11 (1H, d, J 8.5 Hz), 7.19 (1H, t, J 8.0 Hz), 7.34 (2H,s), 7.64-7.67 (2H, m), 7.91 (1H, d, J 3.0 Hz), 8.12 (1H, s), 10.21 (1H,s); Anal. Calcd for C₂₉H₂₁F₃N₆O•0.25H₂O: C, 65.59; H, 4.08; N, 15.83.Found: C, 65.46; H, 4.03; N, 15.76. 10 E 18 IR ν_(max) (Nujol)/cm⁻¹3404, 3313, 3202, 3122, 2923, 2854, 1724, 1639, 1609, 1557, 1456, 1407and 1379; NMR δ_(H) (400 MHz, DMSO) 4.60 (2H, d, J 6.0 Hz), 6.86-6.89(1H, m), 7.25-7.32 (1H, m), 7.33-7.44 (4H, m), 7.67 (2H, s), 7.91 (1H,d, J 3.5 Hz), 8.14-8.16 (1H, m), 9.25 (1H, t, J 6.0 Hz). 11 B 40 IRν_(max) (Nujol)/cm⁻¹ 3327, 3207, 2924, 2854, 1650, 1602, 1583, 1566,1513 and 1487; NMR δ_(H) (400 MHz, DMSO) 3.72 (3H, s), 5.63 (2H, s),6.80 (1H, d, J 7.5 Hz), 6.85-6.89 (3H, m), 7.26 (1H, t, J 7.5 Hz), 7.33(2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11 (1H, s); Anal. Calcd forC₁₆H₁₄N₆O₂•0.25H₂O: C, 58.80; H, 4.47; N, 25.71. Found: C, 58.90; H,4.40; N, 25.75. 12 B 21 IR ν_(max) (Nujol)/cm⁻¹ 3374, 3311, 3202, 1636,1606, 1586, 1530, 1511, 1465, 1439, 1377 and 1343; NMR δ_(H) (400 MHz,DMSO) 6.03 (2H, s), 6.86-6.89 (1H, m), 6.98 (1H, d, J 7.5 Hz), 7.36 (2H,s), 7.60-7.73 (2H, m), 7.92 (1H, d, J 3.5 Hz), 8.14 (1H, s), 8.2 (1H, d,J 8.0 Hz); Anal. Calcd for C₁₅H₁₁N₇O₃•0.35H₂O: C, 52.43; H, 3.43; N,28.54. Found: C, 52.51; H, 3.33; N, 28.21. 13 C 67 IR ν_(max)(Nujol)/cm⁻¹ 3489, 3313, 3191, 1638, 1603, 1505, 1460 and 1378; NMRδ_(H) (400 MHz, DMSO) 5.27 (2H, s), 5.47 (2H, s), 6.50 (1H, t, J 7.5Hz), 6.67-6.78 (2H, m), 6.86 (1H, s), 7.01 (1H, t, J 7.0 Hz), 7.36 (2H,s), 7.90 (1H, d, J 3.0 Hz), 8.12 (1H, s). 14 F 35 IR ν_(max)(Nujol)/cm⁻¹ 3447, 3327, 3205, 2922, 2853, 1725, 1652, 1611 and 1458;NMR δ_(H) (400 MHz, DMSO) 8.13 (1H, d, J 1.0 Hz), 7.90 (1H, d, J 3.5Hz), 7.38 (2H, s), 6.87-6.85 (1H, m), 5.40 (2H, s), 4.18 (2H, q, J 7.0Hz) and 1.21 (3H, t, J 7.0 Hz); Anal. Calcd for C₁₂H₁₂N₆O₂ + 0.2 H₂O: C,49.38; H, 4.28, N, 28.79. Found: C, 49.25; H, 4.09; N, 28.47. 15 B 15 IRν_(max) (Nujol)/cm⁻¹ 3490, 3307, 3189, 2230, 1959, 1728, 1642, 1611,1583, 1565, 1463, 1377, 1283, 1234, 1030 and 761; NMR δ_(H) (400 MHz,DMSO) 5.75 (2H, s), 6.82-6.89 (1H, m), 7.35 (2H, s), 7.57-7.59 (2H, m),7.79-7.81 (2H, m), 7.91 (1H, d, J 3.5 Hz), 8.12 (1H, s). 16 B 6 IRν_(max) (Nujol)/cm⁻¹ 3309, 3184, 2726, 1639, 1608, 1585, 1456, 1377,1026, 1002, 953 and 750; NMR δ_(H) (400 MHz, DMSO) 2.22 (2H, quin, J 7.0Hz), 2.67 (2H, t, J 7.0 Hz), 4.45 (2H, t, J 7.0 Hz), 6.83-6.88 (1H, m),7.23-7.35 (3H, m), 7.66 (1H, dt, J 8.0, 2.0 Hz), 7.89 (1H, dd, J 3.5,1.0 Hz), 8.10-8.13 (1H, m); Anal. calcd for C₁₆H₁₅N₇O•0.6H₂O: C, 57.86;H, 4.92; N, 29.52. Found: C, 57.58; H, 4.53; N, 29.66. 17 B 7 IR ν_(max)(Nujol)/cm⁻¹ 3379, 3336, 3208, 1655, 1604, 1513, 1456, 1325, 11687,1124, 1025 and 755; NMR δ_(H) (400 MHz, DMSO) 5.79 (2H, s), 6.83-6.88(1H, m), 7.36 (2H, s), 7.53 (1H, d, J 7.5 Hz), 7.60 (1H, t, J 7.5 Hz),7.67-7.76 (2H, m), 7.91 (1H, d, J 3.5 Hz), 8.13 (1H, s); Anal. Calcd.for C₁₆H₁₁F₃N₆O: C, 53.34; H, 3.08; N, 23.31. Found: C, 53.38; H, 3.18;N, 23.15. 18 G 100 IR ν_(max) (Nujol)/cm⁻¹ 3451, 3206, 2361, 2261, 1655,1604, 1459, 1378, 1195, 1028 and 774; NMR δ_(H) (400 MHz, DMSO) 5.57(2H, s), 6.57-6.63 (1H, m), 6.65-6.74 (2H, m), 6.83-6.88 (1H, m), 7.14(1H, t, J 7.5 Hz), 7.91 (1H, d, J 3.0 Hz), 8.12 (1H, d, J 1.0 Hz). 19 J77 mp 291.8-292.0° C.; IR ν_(max) (DR)/cm⁻¹ 3436, 3178, 1651, 1615,1398, 1226, 1029 and 977; NMR δ_(H) (400 MHz, DMSO) 15.5-15.3 (1H, brs), 7.84 (1H, d, J 3.5 Hz), 7.07 (2H, br s), 6.48 (1H, dd, J 3.5, J 1.0Hz), 2.44 (3H, s). 20 B 47 mp 213.5.-213.7° C.; IR ν_(max) (DR)/cm⁻¹3300, 3218, 3098, 2957, 2927, 2744, 2368, 1645, 1602, 1570, 1537, 1508,1490, 1438, 1328 and 1233; NMR δ_(H) (400 MHz, DMSO) 7.86 (1H, d, J 3.0Hz), 7.43-736 (1H, m), 7.31 (2H, br s), 7.28-7.15 (3H, m), 6.50 (1H, dd,J 1.0, J 3.5 Hz), 5.68 (2H, s) and 2.45 (3H, s). 21 K 99 IR ν_(max)(DR)/cm⁻¹ 3151, 2360, 1654, 1182, 998, 824, 681, and 572; NMR δ_(H) (400MHz, DMSO) 10.28 (1H, d, J 2.0 Hz) and 9.73 (1H, d, J 2.5 Hz) 22 A 8 IRν_(max) (DR)/cm⁻¹ 3479, 3289, 3169, 1597, 1502, 1226, 1119, 999, 880 and757; NMR δ_(H) (400 MHz, DMSO) 9.43 (1H, s), 9.25 (1H, s), 7.48-7.34(3H, m) 7.30-7.22 (2H, m), 7.21-7.15 (1H, m) and 5.72 (2H, s). 23 B 20mp 187.3-187.7° C.; IR ν_(max) (DR)/cm⁻¹ 3993, 3489, 3319, 3197, 2951,2725, 2353, 1954, 1719, 1633, 1604, 1503, 1420, 1232, 1032 and 740; NMRδ_(H) (400 MHz, DMSO) 2.27 (3H, s) 5.62 (2H, s), 6.82-6.88 (1H, m),7.02-7.16 (3H, m), 7.24 (1H, t, J 7.5 Hz), 7.33 (2H, s), 7.90 (1H, d, J3.5 Hz) 8.12 (1H, s). 24 N 46 mp 196.9-197.1° C.; IR ν_(max) (DR)/cm⁻¹3448, 3321, 3200, 1649, 1616, 1509, 1488; NMR δ_(H) (400 MHz, DMSO)8.49-8.47 (1H, m), 8.12-8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.81-7.77(1H, m), 7.34-7.30 (1H, m), 7.27 (2H, br s), 7.24 (1H, d, J 8.0 Hz),6.86-6.85 (1H, m), 5.77 (2H, s). 25 N 50 IR ν_(max) (DR)/cm⁻¹ 3326,3211, 2956, 2856, 1641, 1612, 1507, 1491; NMR δ_(H) (400 MHz, CDCl₃)8.77-8.76 (1H, m), 8.58-8.56 (1H, m), 8.08 (1H, d, J 3.5 Hz), 7.78 (1H,m), 7.75-7.72 (1H, m), 7.29-7.25 (1H, m), 6.71-6.69 (1H, m), 5.68 (2H,s), 5.37 (2H, br s); Anal. Calcd for C₁₄H₁₁N₇O•0.2H₂O•0.4C₄H₈O₂: C,56.41; H, 4.43, N, 29.52. Found: C, 56.10; H, 4.33; N, 29.52. 26 O 85 mp291.0-291.1° C.; IR ν_(max) (Nujol)/cm⁻¹ 3401, 3317, 3205, 2995, 1714,1646, 1615, 1587, 1483 and 1247; NMR δ_(H) (400 MHz, DMSO) 13.58-13.31(1H, s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.36 (2H, s), 6.87-6.86(1H, m) and 5.29 (2H, s); Anal. Calcd for C₁₀H₈N₆O₃•0.6H₂O: C, 44.32; H,3.42, N, 31.01. Found: C, 44.26; H, 3.07; N, 30.74. 27 B 19 mp209.9-210.1° C.; IR ν_(max) (DR)/cm⁻¹ 3504, 3312, 3201, 2948, 1611,1503, 1435, 1279, 1220, 1025 and 755; NMR δ_(H) (400 MHz, DMSO) 5.69(2H, s), 6.82-6.87 (1H, m), 7.19-7.25 (1H, m), 7.33 (2H, s), 7.37-7.40(3H, m), 7.90 (1H, d, J 3.5 Hz), 8.10-8.13 (1H, m). Anal. Calcd forC₁₅H₁₁N₆OCl•0.2H₂O: C, 54.54; H, 3.48; N, 25.44. Found: C, 54.69; H,3.33; N, 25.09. 28 K 40 IR ν_(max) (DR)/cm⁻¹ 3282, 2852, 1630, 1368,1120, 871and 618; NMR δ_(H) (400 MHz, DMSO) 7.94 (1H, d, J 2.5 Hz),7.45-7.36 (2H, m), 7.29-7.22 (2H, m), 7.21-7.16 (1H, m) and 5.71 (2H,s). 29 B 8 IR ν_(max) (DR)/cm⁻¹ 3999, 3483, 3438, 3310, 3207, 2950,2732, 2452, 1846, 1657, 1486, 1312, 1030 and 754; NMR δ_(H) (400 MHz,DMSO) 4.02 (3H, s), 6.81-6.88 (1H, m), 7.25 (2H, s), 7.88 (1H, d, J 3.5Hz), 8.09-8.11 (1H, m). 30 P 39 IR ν_(max) (Nujol)/cm⁻¹ 3500-3200, 2946,2835, 1700 and 1523; NMR δ_(H) (400 MHz, DMSO) 8.11 (1H, s), 7.89 (1H,d, J 3.5 Hz), 7.69 (1H, s), 7.34 (1H, s), 7.26 (2H, s), 6.87-6.84 (1H,m) and 5.08 (2H, s). 31 P 48 IR ν_(max) (Nujol)/cm⁻¹ 3457, 3313, 1666,1617, 1523 and 1442; NMR δ_(H) (400 MHz, DMSO) 10.68 (1H, s), 8.12 (1H,s), 7.91 (1H, d, J 3.5 Hz), 7.75 (1H, s), 7.45 (1H, d, J 8.0 Hz), 7.37(1H, t, J 8.0 Hz), 7.30 (2H, s), 7.15 (1H, d, J 8.0 Hz), 6.88-6.84 (1H,m and 5.39 (2H, s); Anal. Calcd for C₁₆H₁₂N₇O₂Cl•0.8H₂O: C, 50.02; H,3.57, N, 25.27. Found: C, 50.15; H, 3.48; N, 25.12. 32 N 76 mp191.4-192.0° C.; IR ν_(max) (DR)/cm⁻¹ 3511, 3306, 3194, 2955, 1638,1476; NMR δ_(H) (400 MHz, DMSO) 8.12-8.11 (1H, m), 7.91 (1H, dd, J 3.5,1.0 Hz), 7.66 (1H, dd, J 8.0, 7.0 Hz), 7.27 (2H, br s), 6.87-6.85 (1H,m), 6.73-6.70 (2H, m), 5.69 (2H, s), 3.68 (3H, s); Anal. Calcd forC₁₅H₁₃N₇O₂•0.2C₄H₈O₂: C, 55.66; H, 4.32, N, 28.76. Found: C, 55.88; H,4.17; N, 28.59. 33 B 11 mp 204.1-204.2° C.; IR ν_(max) (DR)/cm⁻¹ 3490,3321, 3200, 2923, 2711, 2490, 1749, 1605, 1502, 1376, 1272, 1034 and761; NMR δ_(H) (400 MHz, DMSO) 5.83 (2H, s), 6.83-6.86 (1H, m), 7.01(1H, dd, J 5.0, 3.5 Hz), 7.16 (1H, dd, J 3.5, 1.0 Hz), 7.34 (2H, s),7.48 (1H, dd, J 5.0, 1.5 Hz), 7.89 (1H, d, J 3.5 Hz), 8.09-8.12 (1H, m).34 Q 30 mp 225-230° C.; IR ν_(max) (DR)/cm⁻¹ 3520, 3344, 1734, 1611,1438, 1240, 996, 833 and 761; NMR δ_(H) (400 MHz, DMSO) 8.26 (1H, d, J3.0 Hz), 8.15 (1H, d, J 3.0 Hz), 7.50-7.44 (2H, br s), 7.42-7.36 (1H,m), 7.29-7.21 (1H, m), 7.21-7.15 (1H, m) and 5.73 (2H, s). 35 H 51 mp174.0-174.2° C.; IR ν_(max) (DR)/cm⁻¹ 3473, 3317, 3188, 2740, 1736,1648, 1243, 1004 and 752; NMR δ_(H) (400 MHz, DMSO) 8.68 (1H, dd, J 4.0,1.5 Hz), 7.99 (1H, dd, J 5.0, 1.0 Hz), 7.43-7.35 (2H, m), 7.31-7.16 (5H,m) and 5.71 (2H, s). 36 C 50 mp 231.7-234.0° C.; IR ν_(max) (DR)/cm⁻¹3498, 3404, 3309, 2931, 1607, 1539, 1498, 1317, 1101 and 1027; NMR δ_(H)(400 MHz, DMSO) 7.86 (1H, dd, J 0.5, 3.5 Hz), 7.24 (2H, br s,), 6.96(1H, t, J 7.8 Hz), 6.50 (1H, dd, J 1.0, 3.5 Hz), 6.48-6.43 (1H, m),6.43-6.38 (1H, m), 6.36 (1H, t, J 1.7 Hz), 5.46 (2H, s), 5.07 (2H, br s)and 2.43 (3H, s). 37 N 60 mp 200.8-218.9° C.; NMR δ_(H) (400 MHz, DMSO)8.12-8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.64 (1H, t, J 7.5 Hz), 7.29(2H, br s), 7.18 (1H, d, J 7.5 Hz), 6.90 (1H, d, J 7.5 Hz), 6.86-6.85(1H, m), 5.70 (2H, s) and 2.42 (3H, s). 38 Q 35 mp 242.0-242.1° C.; IRν_(max) (DR)/cm⁻¹ 3513, 3294, 1570, 1234, 999 and 755; NMR δ_(H) (400MHz, DMSO) 7.96 (1H, s), 7.46-7.34 (3H, m), 7.30-7.13 (3H, m), 5.72 (2H,s) and 2.60 (3H, s). 39 B 26 IR ν_(max) (Nujol)/cm⁻¹ 3464, 3340, 3189,2966, 2748, 1692, 1643 and 1605; NMR δ_(H) (400 MHz, DMSO) 8.11-8.09(1H, m), 7.90 (1H, d, J 3.5 Hz), 7.33-7.24 (4H, m), 7.19-7.12 (2H, m),7.09 (1H, s), 6.86-6.84 (1H, m), 5.64 (2H, s), 4.07 (2H, d, J 6.0 Hz)and 1.33 (9H, s). 40 B 12 IR ν_(max) (Nujol)/cm⁻¹ 3474, 3323, 3184,3006, 2971, 2941, 2837, 1648, 1606 and 1496; NMR δ_(H) (400 MHz, DMSO)8.13-8.10 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.32 (2H, s), 6.98 (1H, d, J9.0 Hz), 6.89-6.84 (2H, m), 6.48 (1H, d, J 3.0 Hz), 5.57 (2H, s), 3.76(3H, s) and 3.62 (3H, s). 41 B 32 mp 213.8-213.9° C.; IR ν_(max)(DR)/cm⁻¹ 3996, 3654, 3507, 3320, 2930, 2562, 2621, 1944, 1837, 1676,1428, 1230, 1095, 1026 and 797; NMR δ_(H) (400 MHz, DMSO) 5.65 (2H, s),6.81-6.86 (1H, m), 7.16 (2H, t, J 8.5 Hz), 7.31 (2H, s), 7.44-7.56 (1H,m), 7.86 (1H, dd, J 3.5, 1.0 Hz), 8.07-8.13 (1H, m). Anal. Calcd forC₁₅H₁₀N₆OF₂: C, 54.88; H, 3.07; N, 25.59. Found: C, 54.57; H, 3.05; N,25.23. 42 Q 29 mp 265.7-26.2° C.; IR ν_(max) (DR)/cm⁻¹ 3491, 3370, 3120,1614, 1232, 972, 753 and 514; NMR δ_(H) (400 MHz, DMSO) 7.72 (1H, s),7.51-7.43 (2H, s), 7.42-7.35 (1H, m), 7.30-7.14 (3H, m), 5.73 (2H, s)and 2.55 (3H, s). 43 H 65 mp 281.1-280.2° C.; IR ν_(max) (DR)/cm⁻¹ 3466,3326, 1641, 1503, 1379, 1240, 1056, and 825; NMR δ_(H) (400 MHz, DMSO)15.5 (1H, br s), 8.6 (1H, dd, J 1.0, 4.0 Hz), 7.96 (1H, dd, J 1.0, 5.0Hz), 7.36 (1H, dd, J 4.0, 5.0 Hz) and 7.0 (2H, br s). 44 S/T 28 IRν_(max) (DR)/cm⁻¹ 3255, 1686, 1590, 1458; NMR δ_(H) (400 MHz, DMSO)11.24 (1H, s), 8.95-8.94 (1H, m), 8.37-8.35 (1H, m), 8.08-8.07 (1H, m),7.96-7.95 (1H, m), 7.68 (1H, d, J 8.0 Hz), 6.85-6.84 (1H, m). 45 A 59 mp190.4-190.8° C.; IR ν_(max) (DR)/cm⁻¹ 3322, 3162, 1665, 1576, 1351,1119, 1000, 809 and 604; NMR δ_(H) (400 MHz, DMSO) 9.44 (1H, s), 9.26(1H, s), 8.24-8.16 (2H, m), 7.95 (1H, s), 7.74-7.63 (2H, m), 7.45 (2H,br s) and 5.87 (2H, s). 46 K 99 IR ν_(max) (Nujol)/cm⁻¹ 2967, 1651 and1463; NMR δ_(H) (400 MHz, DMSO) 8.35-8.24 (3H, s), 8.14-8.11 (1H, m),7.91 (1H, d, J 3.5 Hz), 7.47-7.39 (2H, m), 7.36-7.31 (2H, s), 6.88-6.84(1H, m), 5.67 (2H, s) and 3.98 (2H, q, J 5.5 Hz); Anal. Calcd forC₁₆H₁₅N₇O•2HCl•0.9H₂O: C, 46.82; H, 4.62, N, 23.89. Found: C, 47.10; H,4.40; N, 23.84. 47 B 26 IR ν_(max) (Nujol)/cm⁻¹ 3375, 3194, 2929, 2753,1732, 1657, 1515, 1400 and 1334; NMR δ_(H) (400 MHz, DMSO) 8.14-8.11(1H, m), 7.90 (1H, d, J 3.0 Hz), 7.45-7.29 (6H, m), 6.88-6.84 (1H, m),5.71 (2H, s), 2.95 (3H, s) and 2.85 (3H, s); Anal. Calcd forC₁₈H₁₇N₇O₂•0.5H₂O: C, 58.06; H, 4.87, N, 26.33. Found: C, 58.16; H,4.65; N, 26.06. 48 C 49 mp 265.9-266.0° C.; IR ν_(max) (DR)/cm⁻¹ 3448,3363, 3316, 3189, 1645, 1597, 1511, 1440 and 1103; NMR δ_(H) (400 MHz,DMSO) 8.69 (1H, dd, J 1.2, 3.7 Hz), 7.95 (1H, dd, J 1.2, 5.0 Hz), 7.38(1H, dd, J 3.9, 5.0 Hz), 7.26 (2H, br s), 6.97 (1H, t, J 7.7 Hz),6.48-6.45 (1H, m), 6.44-6.40 (1H, m), 6.36 (1H, t, J 1.7 Hz), 5.5 (2H,s) and 5.11 (2H, br s). 49 B 8 IR ν_(max) (Nujol)/cm⁻¹ 3488, 3319, 2952,1641, 1503 and 1420; NMR δ_(H) (400 MHz, DMSO) 8.49-8.42 (1H, m), 8.14(1H, d, J 1.0 Hz), 7.91 (1H, d, J 3.5 Hz), 7.78-7.71 (2H, m), 7.48-7.32(4H, m), 6.88-6.85 (1H, m), 5.72 (2H, s) and 2.75 (3H, d, J 4.5 Hz). 50C 60 mp 228.2-228.3° C.; IR ν_(max) (DR)/cm⁻¹ 3441, 3318, 3197, 1738,1648, 1515, 1122, 1006, 888 and 747; NMR δ_(H) (400 MHz, DMSO) 9.45 (1H,s), 9.27 (1H, s), 7.44 (2H, br s), 6.97 (1H, t, J 8.0 Hz), 6.49-6.39(2H, m), 6.35 (1H, s), 5.52 (2H, s), and 5.13 (2H, s). 51 N 70 mp182.9-183.1° C.; IR ν_(max) (DR)/cm⁻¹ 3488, 3311, 3199, 2943, 1611,1504; NMR δ_(H) (400 MHz, DMSO) 8.10 (1H, d, J 3.5 Hz), 7.78 (1H, m),7.01 (1H, t, J 9.0 Hz), 6.79 (1H, dt, J 9.0, 3.5 Hz), 6.75-6.73 (1H, m),6.71-6.70 (1H, m), 5.70 (2H, s), 5.38 (2H, br s), 3.71 (3H, s); Anal.Calcd for C₁₆H₁₃N₆O₂F•0.1 H₂O: C, 56.17; H, 3.89, N, 24.56. Found: C,56.27; H, 3.85; N, 24.22. 52 P 70 mp 263.8-264.0° C.; IR ν_(max)(Nujol)/cm⁻¹ 3305, 3192, 1705, 1635 and 1442; NMR δ_(H) (400 MHz, DMSO)11.04 (1H, s), 8.37 (1H, d, J 4.0 Hz), 8.15-8.11 (1H, m), 7.96 (1H, d, J7.0 Hz), 7.91 (1H, d, J 3.0 Hz), 7.79 (1H, dt, J 7.5, 2.0 Hz), 7.32 (2H,s), 7.18-7.11 (1H, m), 6.88-6.85 (1H, m) and 5.46 (2H, s). 53 P 77 mp256.1-256.4° C.; IR ν_(max) (Nujol)/cm⁻¹ 3454, 3311, 2993, 1664, 1488and 1439; NMR δ_(H) (400 MHz, DMSO) 8.86 (1H, t, J 6.0 Hz), 8.50 (1H, d,J 4.5 Hz), 8.12 (1H, s), 7.90 (1H, d, J 3.5 Hz), 7.79 (1H, dt, J 7.5,1.5 Hz), 7.41-7.25 (4H, m), 6.88-6.84 (1H, m) and 5.23 (2H, s), 4.41(2H, d, J 6.0 Hz); Anal. Calcd for C₁₆H₁₄N₈O₂•0.25H₂O: C, 54.16; H,4.12, N, 31.58. Found: C, 54.01; H, 4.03; N, 31.44. 54 P 61 mp292.2-292.3° C.; IR ν_(max) (Nujol)/cm⁻¹ 3433, 3323, 2975, 2941, 1673and 1446; NMR δ_(H) (400 MHz, DMSO) 10.50 (1H, s), 8.13 (1H, s), 7.92(1H, d, J 3.0 Hz), 7.57 (2H, d, J 7.5 Hz), 7.37-7.27 (4H, m), 7.08 (1H,t, J 7.5 Hz), 6.89-6.84 (1H, m) and 5.38 (2H, s). 55 B 18 mp264.5-264.8° C.; IR ν_(max) (DR)/cm⁻¹ 4007, 3489, 3308, 3190, 1649,1552, 1433, 1349, 1227, 1082, 1030 and 729; NMR δ_(H) (400 MHz, DMSO)5.99 (2H, s), 6.84-6.89 (1H, m), 7.39 (2H, s), 7.91 (1H, d, J 3.5 Hz),8.11-8.15 (1H, m), 8.59 (2H, d, J 2.0 Hz), 8.78 (1H, t, J 2.0 Hz). 56 B30 IR ν_(max) (DR)/cm⁻¹ 3508, 3300, 3181, 1611, 1572, 1504, 1420, 1352,1225 and 1030; NMR δ_(H) (400 MHz, DMSO) 8.22-8.16 (2H, m), 7.86 (1H, d,J 3.2 Hz), 7.63-7.72 (2H, m), 7.35 (2H, br s), 6.50 (1H, dd, J 1.0, 3.5Hz), 5.82 (2H, s) and 2.45 (3H, s). 57 B mp 188.8-188.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3492, 3302, 3189, 2951, 1635 and 1505; NMR δ_(H) (400 MHz,DMSO) 8.14-8.10 (1H, m), 7.90 (1H, d, J 3.0 Hz), 7.47-7.32 (3H, m), 7.20(1H, q, J 7.0 Hz), 7.05 (1H, t, J 7.0 Hz), 6.88-6.83 (1H, m) and 5.75(2H, s). 58 B 15 mp 207.0-207.4° C.; IR ν_(max) (Nujol)/cm⁻¹ 3496, 3229,3201, 3057, 2965, 2743, 1785 and 1615; NMR δ_(H) (400 MHz, DMSO)8.13-8.10 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.40-7.27 (4H, m), 7.08 (1H,dt, J 8.5, 3.0 Hz), 6.87-6.84 (1H, m) and 5.66 (2H, s). 59 B 30 mp187.9-188.7° C. IRν_(max) (DR)/cm⁻¹ 3338, 3202, 1659, 1607, 1567, 1523,1457, 1424, 1321, 1204 and 1025; NMR δ_(H) (400 MHz, DMSO) 7.88 (1H, d,J 3.5 Hz), 7.65 (1H, t, J 7.5 Hz), 7.29 (2H, br s), 7.18 (1H, d, J 7.5Hz), 6.89 (1H, d, J 8.0 Hz), 6.51 (1H, d, J 3.0 Hz), 5.69 (2H, s), 2.46(3H, s) and 2.42 (3H, s); Anal. Calcd for C₁₆H₁₅N₇O•0.2H₂O: C, 59.14; H,4.78, N, 30.17. Found: C, 59.37; H, 4.66; N, 29.86. 60 B 33 mp209.7-209.8° C.; IR ν_(max) (DR)/cm⁻¹ 3404, 3330, 3226, 3109, 2961,2926, 2742, 1637, 1601, 1508, and 1474; NMR δ_(H) (400 MHz, DMSO) 7.83(1H, dd, J 0.5, 3.2 Hz), 7.54-7.46 (1H, m), 7.3 (2H, br s), 7.16 (2H, t,J 8.2 Hz), 6.49 (1H, dd, J 1.0, 3.5 Hz), 5.63 (2H, s) and 2.44 (3H, s).61 B 20 mp 193.8-194.1° C.; IR ν_(max) (DR)/cm⁻¹ 3336, 3218, 2980, 2753,2432, 1734, 1654, 1611, 1438, 1381, 1331 and 1224; NMR δ_(H) (400 MHz,DMSO) 7.86 (1H, d, J 3.0 Hz), 7.49 (1H, dd, J 1.5, 5.0 Hz), 7.3 (2H, brs), 7.16 (1H, dd, J 1.0, 3.5 Hz), 7.0 (1H, dd, J 3.5, 5.0 Hz), 6.50 (1H,dd, J 1.0, 3.5 Hz), 5.82 (2H, s) and 2.45 (3H, s). 62 B 40 mp210.4-210.5° C.; IR ν_(max) (DR)/cm⁻¹ 3511, 3300, 3179, 2940, 2740,2688, 1986, 1832, 1734, 1634, 1500 and 1436; NMR δ_(H) (400 MHz, DMSO)7.87 (1H, d, J 3.5 Hz), 7.40-7.37 (3H, m), 7.30 (2H, br s), 7.23-7.18(1H, m), 6.51 (1H, dd, J 1.0, 5.1 Hz), 5.68 (2H, s) and 2.45 (3H, s). 63N 41 mp 201.1-201.2° C.; IR ν_(max) (DR)/cm⁻¹ 3453, 3317, 3195, 1638,1599, 1510, 1434; NMR δ_(H) (400 MHz, DMSO) 8.28 (1H, d, J 6.0 Hz),8.12-8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.29 (2H, br s), 6.91 (1H,dd, J 6.0, 2.5 Hz), 6.87-6.85 (2H, m), 5.71 (2H, s), 3.81 (3H, s). 64 B9 mp 218.0-218.1° C.; IR ν_(max) (DR)/cm⁻¹ 3999, 3376, 3209, 2916, 2747,2326, 1957, 1782, 1610, 1515, 1278, 1023 and 763; NMR δ_(H) (400 MHz,DMSO) 2.42 (3H, s), 5.64 (2H, s), 6.86 (1H, s), 6.91 (1H, d, J 7.5 Hz),7.13 (1H, t, J 7.0 Hz), 7.17-7.26 (2H, m), 7.32 (2H, s), 7.90 (1H, d, J3.5 Hz), 8.12 (1H, s). 65 B 25 mp 208.1-208.2° C.; IR ν_(max)(Nujol)/cm⁻¹ 3347, 3199, 2981, 2932, 2764, 2719, 1660 and 1612; NMRδ_(H) (400 MHz, DMSO) 8.14-8.11 (1H, m), 7.90 (1H, d, J 3.5 Hz),7.41-7.22 (4H, m), 7.15-7.09 (1H, m), 6.87-6.83 (1H, m) and 5.69 (2H,s); Anal. Calcd for C₁₅H₁₀F₂N₆O•0.5H₂O: C, 53.42; H, 3.29, N, 24.92.Found: C, 53.72; H, 3.06; N, 24.77. 66 W 25 mp 243.4-243.9° C.; IRν_(max) (Nujol)/cm⁻¹ 4008, 3483, 3316, 3196, 1734, 1599 and 1505; NMRδ_(H) (400 MHz, DMSO) 8.32 (1H, dd, J 9.0, 3.0 Hz), 8.21 (1H, d, J 3.0Hz), 8.12-8.10 (1H, m), 7.68 (1H, d, J 3.5 Hz), 7.31 (1H, d, J 9.0 Hz),7.00 (2H, s), 6.85-6.82 (1H, m), 5.94 (2H, s) and 3.93 (3H, s); Anal.Calcd for C₁₆H₁₃N₇O₄: C, 52.32; H, 3.57, N, 26.68. Found: C, 52.16; H,3.56; N, 26.67. 67 B 32 mp 252.9-253.0° C.; IR ν_(max) (DR)/cm⁻¹ 3511,33260, 2945, 1732, 1626, 1573, 1499, 1422, 1327 and 1222; NMR δ_(H) (400MHz, DMSO) 8.4 (1H, d, J 4.5 Hz), 7.87 (1H, d, J 3.0 Hz), 7.77-7.71 (2H,m) 7.47-7.38 (2H, m), 7.3 (2H, br s), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.70(2H, s), 2.75 (3H, d, J 4.5 Hz)and 2.45 (3H, s). 68 R 58 mp 228.1-229.3°C.; IR ν_(max) (Nujol)/cm⁻¹ 3508, 3263, 2990, 2946, 2837, 1646 and 1419;NMR δ_(H) (400 MHz, DMSO) 8.29 (1H, t, J 6.0 Hz), 8.14-8.09 (1H, m),7.90 (1H, d, J 3.5 Hz), 7.33 (2H, s), 7.29 (1H, t, J 7.5 Hz), 7.21-7.09(3H, m), 6.88-6.83 (1H, m), 5.64 (2H, s), 4.20 (1H, d, J 6.0 Hz) and1.83 (3H, s); Anal. Calcd for C₁₈H₁₇N₇O₂•0.25H₂O: C, 58.77; H, 4.79, N,26.65. Found: C, 58.86; H, 4.54; N, 26.24. 69 X 2 NMR δ_(H) (400 MHz,DMSO) 8.53 (1H, s), 7.69 (1H, s), 7.58 (2H, br s), 7.45-7.36 (1H, m),7.29-7.22 (2H, m), 7.21-7.15 (1H, m) and 5.73 (2H, s); Retention time1.14 min. 70 N 39 NMR δ_(H) (400 MHz, DMSO) 8.45 (1H, d, J 5.0, 1.0 Hz),8.13-8.12 (1H, m), 7.91 (1H, dd, J 3.5, 1.0 Hz), 7.51-7.48 (2H, m), 7.31(2H, br s), 6.87-6.85 (1H, m), 5.80 (2H, s); Retention time 1.75 min. 71N 65 mp 228.7-228.9° C.; IR ν_(max) (DR)/cm⁻¹ 3408, 3326, 3210, 1648,1614, 1511; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m), 8.02-7.96 (1H,m), 7.92 (1H, d, J 3.5 Hz), 7.33 (2H, br s), 7.20 (1H, dd, J 7.5, 2.0Hz), 7.12 (1H, dd, J 8.0, 2.0 Hz), 6.87 (1H, dd, J 3.5, 1.0 Hz), 5.75(2H, s); Anal. Calcd for C₁₄H₁₁N₇OF•0.2H₂O•0.1C₄H₁₀O₂: C, 53.66; H,3.57, N, 30.42. Found: C, 53.68; H, 3.44; N, 30.24. 72 B 28 mp195.4-196.5° C.; IR ν_(max) (DR)/cm⁻¹ 3328, 3210, 2956, 2836, 2740,1736, 1648, 1608, 1438, 1322 and 1250; NMR δ_(H) (400 MHz, DMSO) 7.87(1H, d, J 3.5 Hz), 7.33-7.25 (3H, m), 7.05 (1H, d, J 7.5 Hz), 6.88 (1H,td, J 1.0, 7.5 Hz), 6.87 (1H, dd, J 2.0, 7.5 Hz), 6.50 (1H, dd, J 1.0,3.5 Hz), 5.58 (2H, s), 3.83 (3H, s) and 2.45 (3H, s). 73 B 28 mp178.7-179.3° C.; IR ν_(max) (DR)/cm⁻¹ 3468, 3346, 3172, 2988, 2747,2130, 1943, 1696, 1610, 1418, 1330, and 1177; NMR δ_(H) (400 MHz, DMSO)7.86 (1H, d, J 3.01 Hz), 7.34-7.26 (4H, m), 7.20-7.10 (2H, m) 7.09 (1H,s), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.63 (2H, s), 4.2 (2H, d, J 6.0 Hz),2.45 (2H, s) and 1.34 (9H, s). 74 C 40 mp 214.6-215.2° C.; IR ν_(max)(DR)/cm⁻¹2877, 1653, 1596, 1523, 1470, 1355, 1284, 1241, 1210 and 1109;NMR δ_(H) (400 MHz, DMSO) 7.87 (1H, d, J 3.0 Hz), 7.16 (1H, t, J 7.0Hz), 7.0-6.75 (3H, m), 6.51 (1H, d, J 3.0 Hz), 5.58 (2H, s) and 2.45(3H, s). 75 C 3 NMR δ_(H) (400 MHz, DMSO) 4.74 (4H, s), 5.33 (2H, s),5.62 (2H, d, J 2.0 Hz), 5.71 (1H, t, J 2.0 Hz), 6.83-6.88 (1H, m), 7.29(2H, s), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.10-8.12 (1H, m); Retention time2.95 min. 76 K 100 IR ν_(max) (DR)/cm⁻¹ 3011, 1650, 1525, 1468, 1351,1284 and 1210; NMR δ_(H) (400 MHz, CD₃OD) 8.36 (1H, d, J 3.5 Hz),7.53-7.42 (4H, m), 6.72 (1H, dd, J 1.0 Hz, 3.5 Hz), 5.76 (2H, s), 4.11(2H, s) and 2.61 (3H, s). 77 W 25 mp 212.1-214.3° C.; IR ν_(max)(DR)/cm⁻¹ 4007, 3474, 3323, 3199, 2934, 2747, 2105, 1647, 1603, 1492,1245, 1028 and 754; NMR δ_(H) (400 MHz, DMSO) 3.82 (3H, s), 5.60 (2H,s), 6.78-6.93 (3H, m), 7.05 (1H, d, J 8.5 Hz), 7.24-7.38 (3H, m), 7.90(1H, d, J 3.0 Hz), 8.12 (1H, s). 78 B 21 IR ν_(max) (DR)/cm⁻¹ 4002,3482, 3313, 3201, 2938, 2739, 2339, 2107, 1936, 1731, 1650, 1436, 1253,1082 and751; NMR δ_(H) (400 MHz, DMSO) 5.82 (2H, s), 6.84-6.88 (1H, m),7.38 (2H, s), 7.58 (1H, t, J 9.0 Hz), 7.90 (1H, t, J 3.0 Hz), 8.12 (1H,d, J 1.0 Hz), 8.23-8.28 (1H, m), 8.29-8.35 (1H, m). 79 C 64 mp308.2-308.3° C.; IR ν_(max) (DR)/cm⁻¹ 4013, 3456, 3322, 3193, 2958,2745, 2103, 1861, 1653, 1516, 1237, 1026 and 777; NMR δ_(H) (400 MHz,DMSO) 4.95 (2H, s), 5.56 (2H, s), 6.15-6.20 (1H, m), 6.44-6.51 (1H, m),6.84-6.93 (2H, m), 7.34 (2H, s), 7.91 (1H, d, J 3.0 Hz), 8.12 (1H, d, J1.0 Hz). 80 Y 10 NMR δ_(H) (400 MHz, DMSO) 8.84 (1H, br s), 7.46-7.35(2H, m), 7.32-7.14 (4H, m) and 5.72 (2H, s); Retention time 0.84 min. 81B 47 mp 229.3-229.4° C.; IR ν_(max) (DR)/cm⁻¹ 3514, 3292, 3166, 1614,1503; NMR δ_(H) (400 MHz, DMSO) 7.88-7.84 (2H, m), 7.47 (1H, d, J 8.0Hz), 7.31 (2H, br s), 7.22 (1H, d, J 7.0 Hz), 6.52-6.51 (1H, m), 5.75(2H, s), 2.46 (3H, s); Anal. Calcd for C₁₅H₁₂N₇OCl•0.1H₂O: C, 52.44; H,3.58, N, 28.54. Found: C, 52.62; H, 3.59; N, 28.20. 82 H 36 mp205.0-205.3° C.; NMR δ_(H) (400 MHz, DMSO) 7.97-7.85 (5H, m), 7.46-7.41(3H, m), 7.32 (2H, br s), 7.13 (1H, d, J 8.5 Hz), 6.53-6.52 (1H, m),5.85 (2H, s), 2.46 (3H, s). 83 C 19 mp 252.8-253.3° C.; NMR δ_(H) (400MHz, MeOD) 8.21 (1H, d, J 3.0 Hz), 7.98 (1H, d, 3.5 Hz), 7.62-7.52 (2H,m), 7.37-7.31 (2H, m) and 5.81 (2H, s); Retention time 0.83 min. 84 C 53mp 235.8-236.5° C.; IR ν_(max) (DR)/cm⁻¹ 3309, 2836, 2033, 1823, 1651,1505, 1468, 1354, 1250 and 1209; NMR δ_(H) (400 MHz, CD₃OD) 8.18 (1H, d,J 4.0 Hz), 7.47-7.37 (3H, m), 6.61 (1H, dd, J 1.0, 3.5 Hz), 5.82 (2H, s)and 2.57 (3H, s). 85 R 72 mp 215.9-217.5° C.; IR ν_(max) (Nujol)/cm⁻¹3308, 2955, 2869, 1634, 1505 and 1435; NMR δ_(H) (400 MHz, DMSO) 8.27(1H, t, J 5.5 Hz), 8.13 (1H, d, J 1.0 Hz), 7.91 (1H, d, J 3.5 Hz), 7.36(2H, s), 7.31 (1H, t, J 7.5 Hz), 7.17 (2H, t, J 7.5 Hz), 7.09 (1H, s),6.89-6.84 (1H, m), 5.64 (2H, s), 4.21 (2H, d, J 6.0 Hz), 1.93 (2H, s)and 0.79 (6H, d, J 6.5 Hz). 86 B 51 NMR δ_(H) (400 MHz, DMSO) 8.84 (1H,d, J 5.5 Hz), 8.14 (1H, d, J 2.0 Hz), 8.08 (1H, dd, J 5.5, 1.0 Hz), 7.89(1H, d, J 5.5 Hz), 7.34 (2H, br s), 6.53-6.52 (1H, m), 5.98 (2H, s),2.46 (3H, s); Retention time 1.85 min. 87 Z 73 NMR δ_(H) (400 MHz, DMSO)9.10 (1H, s), 8.69 (1H, s), 8.05 (1H, d, J 5.5 Hz), 7.89 (1H, d, J 3.0Hz), 7.32 (2H, br s), 6.59-6.57 (1H, m), 6.53-6.51 (1H, m), 6.37-6.36(1H, m), 5.60 (2H, s), 2.46 (3H, s); M/Z 339 (M + H)⁺; Retention time0.79 min. 88 B 11 mp 258.8-259.0° C.; IR ν_(max) (DR)/cm⁻¹ 4014, 3316,3204, 2966, 2746, 2561, 2106, 1962, 1606, 1526, 1436, 1351, 1029 and758; NMR δ_(H) (400 MHz, DMSO) 2.46 (3H, s), 5.79 (2H, s), 6.86-6.88(1H, m), 7.23 (1H, d, J 7.5 Hz), 7.30-7.50 (3H, m), 7.81 (1H, d, J 8.0Hz), 7.91 (1H, d, J 3.5 Hz), 8.13-8.15 (1H, m). Anal. Calcd forC₁₆H₁₃N₇O₃: C, 54.70; H, 3.73; N, 27.89. Found: C, 54.70; H, 3.77; N,27.48. 89 C 57 mp 247.1-247.2° C.; IR ν_(max) (DR)/cm⁻¹ 3322, 1740,1600, 1240, 1167, 959 and 770; NMR δ_(H) (400 MHz, DMSO) 2.10 (3H, s),4.93 (2H, s), 5.56 (2H, s), 6.11 (1H, d, J 6.5 Hz), 6.58 (1H, d, J 8.0Hz), 6.80 (1H, t, J 7.5 Hz), 6.85-6.87 (1H, m), 7.35 (2H, s), 7.90 (1H,d, J 3.5 Hz), 8.12-8.14 (1H, m). 90 C 38 mp 268.5-269.1° C.; IR ν_(max)(DR)/cm⁻¹ 4010, 3451, 3317, 3182, 2957, 2749, 2104, 1844, 1652, 1608,1487, 1335, 1025 and 764; NMR δ_(H) (400 MHz, DMSO) 1.99 (3H, s), 4.89(2H, s), 5.47 (2H, s), 6.36-6.43 (2H, m), 6.84-6.89 (2H, m), 7.35 (2H,s), 7.91 (1H, d, J 3.5 Hz) 8.12-8.14 (1H, m). 91 B 15 mp 284.3-284.5°C.; IR ν_(max) (DR)/cm⁻¹ 3321, 3216, 1612, 1031, 765 and 552; NMR δ_(H)(400 MHz, DMSO) 8.12 (1H, d, J 1.0 Hz), 7.88 (1H, d, J 3.5 Hz), 7.35(2H, br s), 6.85 (1H, dd, J 3.5, 1.5 Hz), 5.44 (2H, s), 2.52 (3H, s) and2.25 (3H, s) 92 B 8 mp 267.9-268.5° C.; NMR δ_(H) (400 MHz, DMSO) 2.32(3H, s), 5.69 (2H, s), 6.85-6.89 (1H, s), 7.04-7.10 (1H, m), 7.33-7.54(4H, m), 7.90 (1H, d, J 3.5 Hz), 8.13-8.15 (1H, m). 93 B 4 IR ν_(max)(Nujol)/cm⁻¹ 3316, 3193, 2926, 2851, 1637, 1508 and 1437; NMR δ_(H) (400MHz, DMSO) 8.11-8.09 (1H, m), 7.89 (1H, dd, J 3.5, 1.0 Hz), 7.27 (2H,s), 6.86-6.83 (1H, m), 4.26 (2H, d, J 7.5 Hz), 2.04-1.90 (1H, m),1.72-1.50 (5H, m) and 1.25-0.95 (5H, m). 94 B 15 mp 237.8-238.0° C.; NMRδ_(H) (400 MHz, DMSO) 2.49 (3H, s), 5.76 (2H, s), 6.84-6.88 (1H, m),7.28 (1H, dd, J 8.5, 1.5 Hz), 7.30-7.42 (3H, m), 7.91 (1H, d, J 3.5 Hz),7.97 (1H, d, J 8.5 Hz), 8.11-8.14 (1H, m). Anal. Calcd forC₁₆H₁₃N₇O₃•0.1H₂O: C, 54.42; H, 3.77; N, 27.77. Found: C, 54.73; H,3.78; N, 27.40. 95 N 32 mp 249.8-250.0° C.; IR ν_(max) (DR)/cm⁻¹ 3437,3317, 3210, 2964, 2865, 1610, 1508; NMR δ_(H) (400 MHz, DMSO) 8.19-8.17(1H, m), 8.12 (1H, m), 7.92-7.91 (1H, m), 7.66-7.63 (1H, m), 7.24-7.20(3H, m), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.80 (2H, s), 2.44 (3H, s). 96 B4 mp 226.6-226.9° C.; NMR δ_(H) (400 MHz, DMSO) 2.32 (3H, s), 5.98 (2H,s), 6.84 (1H, s), 6.85-6.90 (1H, m), 7.35 (2H, s), 7.43 (1H, d, J 7.5Hz), 7.91 (1H, d, J 7.5 Hz), 8.07-8.15 (2H, m). 97 C 63 mp 245.3-246.1°C.; IR ν_(max) (DR)/cm⁻¹ 4010, 3406, 3320, 3198, 2929, 2746, 1608, 1507,1414, 1285, 1022 and 753; NMR δ_(H) (400 MHz, DMSO) 2.00 (3H, s), 4.86(2H, s), 5.42 (2H, s), 6.54 (1H, d, J 8.0 Hz), 6.82-6.85 (1H, m), 6.90(1H, dd, J 8.0, 2.0 Hz), 6.92-6.95 (1H, m), 7.29 (2H, s), 7.88 (1H, d, J3.5 Hz), 8.09-8.12 (1H, m). Anal. Calcd for C₁₆H₁₅N₇O•0.2H₂O: C, 59.14;H, 4.78; N, 30.17. Found: C, 59.44; H, 4.74; N, 29.82. 98 O 98 IRν_(max) (Nujol)/cm⁻¹ 3324, 3206, 1698, 1650 and 1611; NMR δ_(H) (400MHz, DMSO) 13.56-12.46 (1H, s), 8.13-8.11 (1H, s), 7.92-7.84 (3H, m),7.56-7.31 (3H, m), 6.87-6.85 (1H, m) and 7.74 (2H, s). 99 P 66 IRν_(max) (Nujol)/cm⁻¹ 3324, 1644, 1491 and 1417; NMR δ_(H) (400 MHz,DMSO) 8.12 (1H, s), 7.98-7.93 (1H, s), 7.91 (1H, d, J 3.0 Hz), 7.81 (1H,d, J 6.5 Hz), 7.77 (1H, s), 7.47-7.29 (5H, m), 6.86 (1H, s) and5.77-5.68 (2H, m). 100 B 13 mp 285.7-285.9° C.; IR ν_(max) (DR)/cm⁻¹3345, 3197, 1664, 1613, 1116, 766 and 600; NMR δ_(H) (400 MHz, DMSO)8.13-8.02 (1H, m) 7.90 (1H, d, J 3.5 Hz), 7.37-7.27 (3H, m), 6.86 (1H,dd, J 3.5, 2.0 Hz), 5.67 (2H, s) and 2.52 (3H, s). 101 AA 32 mp279.9-280.3° C.; NMR δ_(H) (400 MHz, DMSO) 8.33 (3H, br s), 7.93 (1H, d,J 2.0 Hz), 7.51-7.39 (2H, m), 7.39-7.31 (3H, m), 5.69 (2H, s) and 3.98(2H, q, J 5.5 Hz). 102 P 23 IR ν_(max) (Nujol)/cm⁻¹ 3480, 3322, 3202,283, 1608 and 1506; NMR δ_(H) (400 MHz, DMSO) 8.12 (1H, s), 7.90 (1H, d,J 3.5 Hz), 7.47-7.25 (5H, m), 6.87-6.84 (1H, m), 5.72 (2H, s), 3.77-3.61(1H, s), 2.76 (3H, s), 1.10 (3H, s) and 0.99 (3H, s). 103 P 58 IRν_(max) (Nujol)/cm⁻¹ 3298, 2972, 1635 and 1418; NMR δ_(H) (400 MHz,DMSO) 8.21 (1H, d, J 7.5 Hz), 8.12 (1H, s), 7.91 (1H, d, J 3.0 Hz),7.82-7.74 (2H, m), 7.48-7.29 (4H, m), 6.86 (1H, s), 5.71 (2H, s),4.13-4.01 (1H, m) and 1.13 (6H, d, J 6.5 Hz). 104 C 10 mp 249.9-250.5°C.; NMR δ_(H) (400 MHz, DMSO) 2.07 (3H, s), 5.06 (2H, s), 5.43 (2H, s),6.60-6.65 (2H, m), 6.81-6.89 (2H, m), 7.37 (2H, s), 7.90 (1H, dd, J 3.5,1.0 Hz), 8.12 (1H, d, J 1.0 Hz). Anal. Calcd for C₁₆H₁₅N₇O•0.2H₂O: C,59.14; H, 4.78; N, 30.17. Found: C, 59.53; H, 4.75; N, 29.87. 105 B 16mp 263.2-263.5° C.; IR ν_(max) (DR)/cm⁻¹ 3499, 3307, 3192, 2958, 2238,1610, 1490; NMR δ_(H) (400 MHz, DMSO) 8.73 (1H, d, J 5.0 Hz), 8.13-8.12(1H, m), 7.92-7.90 (1H, m), 7.85-7.81 (2H, m), 7.30 (2H, br s),6.87-6.86 (1H, m), 5.87 (2H, s). 106 B 16 mp 288.1-288.2° C.; IR ν_(max)(DR)/cm⁻¹ 3324, 3196, 1609, 1489, 1166, 1004, 798 and 550; NMR δ_(H)(400 MHz, DMSO) 8.59 (1H, s), 8.44 (1H, s), 8.12 (1H, s), 7.90 (1H, d, J3.5 Hz), 7.31 (2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.81 (2H, s) and2.48 (3H, s). 107 B 22 mp 276.4-277.4° C.; IR ν_(max) (DR)/cm⁻¹ 3443,3324, 3202, 1610, 1324, 1229, 1030 and 788; NMR δ_(H) (400 MHz, DMSO)9.01 (1H, dd, J 4.0, 2.0 Hz), 8.45 (1H, dd, J 8.5, 2.0 Hz), 8.14-8.12(1H, m), 7.97 (1H, d, J 8.0 Hz), 7.93 (1H, d, J 3.5 Hz), 7.64 (1H, 1H,dd, J 8.5, 4.0 Hz), 7.52 (1H, t, J 7.0 Hz), 7.31 (2H, br s), 7.15 (1H,d, J 7.5 Hz), 6.87 (1H, dd, J 3.5, 2.0 Hz) and 6.31 (2H, s). 108 B 30 mp215.0-215.3° C.; IR ν_(max) (DR)/cm⁻¹ 3325, 3198, 1612, 1246, 1026, 727and 567; NMR δ_(H) (400 MHz, DMSO) 8.14-8.12 (1H, m), 7.91 (1H, dd, J3.5, 1.0 Hz), 7.90-7.85 (2H, m), 7.52 (1H, s), 7.51-7.46 (3H, m), 7.36(2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), and 5.81 (2H, s). 109 Q 23 mp289.8-289.9° C.; IR ν_(max) (DR)/cm⁻¹ 3350, 2924, 2863, 1981, 1723,1618, 1351, 1100, 974, 766 and 524; NMR δ_(H) (400 MHz, DMSO) 8.23-8.16(2H, m), 7.77-7.62 (3H, m), 7.49 (2H, br s), 5.88 (2H, s) and 2.56 (3H,s). 110 B 31 mp 247.4-247.5° C.; IR ν_(max) (DR)/cm⁻¹ 3999, 3470, 3316,3198, 2929, 2744, 2345, 2103, 1924, 1837, 1773, 1649, 1435, 1355, 1237,1029 and 768; NMR δ_(H) (400 MHz, DMSO) 5.79 (2H, s), 6.85-6.87 (1H, m),7.36 (2H, s), 7.56 (1H, dd, J 8.5, 2.0 Hz), 7.76 (1H, d, J 8.0 Hz), 7.91(1H, dd, J 3.5, 1.0 Hz), 8.04 (1H, d, J 2.0 Hz), 8.12-8.13 (1H, m).Anal. Calcd for C₁₅H₁₀N₇O₃Cl: C, 48.47; H, 2.71; N, 26.36. Found: C,48.63; H, 2.80; N, 26.22. 111 B 14 mp 244.1-244.6° C.; NMR δ_(H) (400MHz, DMSO) 5.84 (2H, s), 6.85-6.89 (1H, m), 7.37 (2H, s), 7.54 (1H, dd,J 9.5, 1.5 Hz), 7.84 (1H, t, J 1.0 Hz), 7.92 (1H, d, J 3.5 Hz), 8.08(1H, dd, J 9.0, 1.0 Hz), 8.12-8.15 (1H, m). Anal. Calcd forC₁₅H₁₀N₈O₂•0.75C₃H₇NO: C, 53.25; H, 3.95; N, 31.50. Found: C, 53.08; H,3.79; N, 31.38. 112 B 28 mp 190.4-191.4° C.; IR ν_(max) (DR)/cm⁻¹ 3482,3308, 3194, 2940, 2880, 1610, 1508; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12(1H, m), 7.92 (1H, d, J 3.5 Hz), 7.78 (1H, t, J 8.0 Hz), 7.35-7.32 (3H,m), 7.04 (1H, d, J 7.5 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 5.75 (2H, s),4.43 (2H, s), 3.33 (3H, s). 113 B 39 IR ν_(max) (Nujol)/cm⁻¹ 3499, 3316,3193, 2946, 1651 and 1509; NMR δ_(H) (400 MHz, DMSO) 8.13-8.10 (1H, m),7.90 (1H, d, J 3.5 Hz), 7.39-7.26 (7H, m), 6.87-6.84 (1H, m) and 5.67(2H, s); Anal. Calcd for C₁₅H₁₂N₆O•0.75H₂O: C, 58.91; H, 4.45, N, 27.48.Found: C, 58.84; H, 4.10; N, 27.32. 114 C 67 mp 256.7-257.1° C.; IRν_(max) (DR)/cm⁻¹ 4003, 3452, 3324, 3203, 2950, 2746, 2102, 1733, 1654,1516, 1420, 1305, 1221, 1106, 1024 and 761; NMR δ_(H) (400 MHz, DMSO)5.38 (2H, s), 5.51 (2H, s), 6.46 (1H, dd, J 8.5, 2.5 Hz), 6.58 (1H, d, J2.0 Hz), 6.84-6.87 (1H, m), 7.15 (1H, d, J 8.0 Hz), 7.32 (2H, s), 7.91(1H, dd, J 3.5, 1.0 Hz), 8.11-8.13 (1H, m). Anal. Calcd forC₁₅H₁₂N₇OCl•0.3H₂O: C, 51.90; H, 3.66; N, 28.24. Found: C, 52.12; H,3.48; N, 27.86. 115 B 12 NMR δ_(H) (400 MHz, DMSO) 8.84 (1H, d, J 5.5Hz), 8.15-8.12 (2H, m), 8.08-8.06 (1H, m), 7.92-7.91 (1H, m), 7.32 (2H,br s), 6.87 (1H, dd, J 3.5, 1.5 Hz), 5.99 (2H, s); Retention time 1.28min. 116 Z 87 NMR δ_(H) (400 MHz, DMSO) 9.08 (1H, br s), 8.66 (1H, brs), 8.13-8.12 (1H, m), 8.06-8.04 (1H, m), 7.93-7.91 (1H, m), 7.32 (2H,br s), 6.87-6.86 (1H, m), 6.60-6.58 (1H, m), 6.38-6.37 (1H, m), 5.61(2H, s); M/Z 325 (M + H)⁺. 117 B 9 IR ν_(max) (DR)/cm⁻¹ 3491, 3310,3198, 2976, 1612; NMR δ_(H) (400 MHz, DMSO) 8.14-8.13 (1H, m), 7.99-7.98(1H, m), 7.93-7.91 (1H, m), 7.80-7.79 (1H, m), 7.34 (2H, br s),6.88-6.86 (1H, m), 5.90 (2H, s), 2.57 (3H, s). 118 Z 91 NMR δ_(H) (400MHz, DMSO) 13.45 (1H, br s), 9.50 (1H, br s), 8.15-8.14 (1H, m), 7.92(1H, d, J 3.5 Hz), 7.39 (2H, br s), 6.87-6.86 (1H, m), 6.56 (1H, br s),6.15 (1H, br s), 5.67 (2H, s), 2.39 (3H, s); M/Z 339 (M + H)⁺. 119 B 15mp > 230° C.; IR ν_(max) (DR)/cm⁻¹ 3993, 3509, 3314, 3195, 2997, 2950,2682, 2561, 2101, 1943, 1780, 1613, 1501, 1433, 1345, 1100, 1027, 889and 780; NMR δ_(H) (400 MHz, DMSO) 6.00 (2H, s), 6.85-6.90 (1H, m), 7.05(1H, d, J 8.5 Hz), 7.37 (2H, s), 7.78 (1H, dd, J 8.5, 2.0 Hz), 7.91 (1H,d, J 3.5 Hz), 8.14 (1H, d, J 1.0 Hz), 8.27 (1H, d, J 2.5 Hz). Anal.Calcd for C₁₅H₁₀N₇O₃Cl•0.3H₂O: C, 47.77; H, 2.83; N, 26.00. Found: C,47.65; H, 2.71; N, 25.85. 120 C 19 mp 211.4-211.6° C.; IR ν_(max)(DR)/cm⁻¹ 4015, 3325, 3218, 2969, 2878, 2101, 1653, 1508, 1423, 1275,1023, 834 and 761; NMR δ_(H) (400 MHz, DMSO) 5.45 (2H, s), 5.60 (2H, s),6.51 (1H, dd, J 8.0, 2.0 Hz), 6.70-6.79 (2H, m), 6.83-6.89 (1H, m), 7.38(2H, s), 7.90 (1H, d, J 3.5 Hz), 8.12 (1H, s). 121 B 13 mp 292.3-292.4°C.; IR ν_(max) (DR)/cm⁻¹ 3324, 3207, 2098, 1602, 1527, 1352, 1024 and813; NMR δ_(H) (400 MHz, CDCl3) 8.10 (1H, d, J 3.0 Hz), 7.79 (1H, d, J1.5 Hz), 7.64 (2H, d, J 8.5 Hz), 7.49 (2H, d, J 8.5 Hz), 6.71 (1H, dd, J3.5, 1.5 Hz), 5.71 (2H, s) and 5.38 (2H, br s). 122 A 50 mp 227.5-228.5°C.; IR ν_(max) (DR)/cm⁻¹, 3265, 1701, 1521, 1480, 1413, 1355, 1309, 1204and 1147; NMR δ_(H) (400 MHz, DMSO) 8.11 (1H, d, J 1.0 Hz), 7.9 (1H, d,J 3.5 Hz), 7.3 (2H, br s), 7.04 (1H, d, J 2.0 Hz), 6.90 (1H, d, J 8.0Hz), 6.85 (1H, dd, J 1.5, 3.5 Hz), 6.79 (1H, dd, J 2.0, 8.0 Hz), 5.57(2H, s), 3.71 (3H, s,) and 3.72 (3H, s). 123 B 35 mp 214.6-216.2° C.; IRν_(max) (DR)/cm⁻¹ 3512, 3295, 3173, 2988, 2736, 2415, 1636, 1437, 1340and 1228; NMR δ_(H) (400 MHz, DMSO) 7.97 (1H, d, J 8.5 Hz), 7.87 (1H, d,J 3.0 Hz), 7.40 (1H, d, J 1.0 Hz), 7.31 (2H, br s), 7.27 (1H, dd, J 1.5,8.0 Hz), 6.51 (1H, dd, J 1.0, 3.5 Hz), 5.74 (2H, s), 2.48 (3H, s) and2.46 (3H, s). 124 C 65 mp 215.7-216.7° C.; IR ν_(max) (DR)/cm⁻¹3328,2928, 2424, 2345, 1609 and 1263; NMR δ_(H) (400 MHz, DMSO) 7.85 (1H, d,J 3.5 Hz), 7.26 (2H, br s), 6.93 (1H, d, J 1.5 Hz), 6.89 (1H, dd, J 2.0,8.0 Hz), 6.54 (1H, d, J 8.0 Hz), 6.49 (1H, J 1.0, 3.5 Hz), 5.40 (2H, s),4.89 (2H, br s), 2.45 (3H, s) and 2.27 (3H, s). 125 B 29 mp 221.5-221.6°C.; IR ν_(max) (DR)/cm⁻¹ 3506, 3294, 3178, 2683, 1613, 1315, 1027 and697; NMR δ_(H) (400 MHz, DMSO) 8.13-8.11 (1H, m), 7.90 (1H, d, J 4.5Hz), 7.38 (2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.18-6.16 (1H, m),5.70 (2H, s) and 2.36 (3H, s). 126 N 26 mp 229.6-230.3° C.; IR ν_(max)(DR)/cm⁻¹ 3317, 3198, 1602, 1499; NMR δ_(H) (400 MHz, DMSO) 8.44-8.43(1H, m), 8.31 (1H, d, J 5.0 Hz), 8.14-8.13 (1H, m), 7.92 (1H, d, J 3.0Hz), 7.35 (2H, br s), 6.88-6.86 (1H, m), 6.70 (1H, d, J 5.0 Hz), 5.71(2H, s), 2.39 (3H, s). 127 B 13 mp 275.0-273.3° C.; IR ν_(max) (DR)/cm⁻¹3449, 3310, 3202, 1605, 1487, 1420, 1023, 836, 760 and 551; NMR δ_(H)(400 MHz, DMSO) 8.15-8.11 (1H, m), 8.07 (1H, d, J 9.0 Hz), 7.91 (1H, d,J 3.5 Hz), 7.68 (1H, dd, J 9.0, 6.5 Hz), 7.38-7.29 (3H, m), 6.86 (1H,dd, J 3.5, 1.5 Hz) and 6.15 (2H, s). 128 B 16 mp 129.1-131.0° C.; IRν_(max) (DR)/cm⁻¹ 3993, 3470, 3310, 3197, 1610, 1508, 1420, 1239, 1002and 796; NMR δ_(H) (400 MHz, DMSO) 8.74 (1H, d, J 1.5 Hz), 8.61 (1H, d,J 2.5 Hz), 8.57-8.54 (1H, m), 8.13-8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz),7.31 (2H, br s), 6.86 (1H, dd, J 3.5, 2.0 Hz) and 5.88 (2H, s). 129 B 20mp 266.5-266.7° C.; IR ν_(max) (DR)/cm⁻¹ 4018, 3487, 3310, 3193, 2744,1636, 1585, 1539, 1507, 1437, 1347, 1266, 1238 and 1196; NMR δ_(H) (400MHz, DMSO) 8.15 (1H, dd, J 2.5, 7.5 Hz), 8.12 (1H, d, J 1.0 Hz), 7.90(1H, d, J 3.5 Hz), 7.73-7.68 (1H, m), 7.58 (1H, dd, J 11.3, 8.8 Hz),7.36 (2H, br s), 6.88 (1H, dd, J 1.5, 3.5 Hz) and 5.78 (2H, s). 130 H 32mp 149.0-149.6° C.; IR ν_(max) (DR)/cm⁻¹ 4072, 3332, 3198, 1654, 1604,1348, 1237, 1111, 1012, 775, 691 and 570; NMR δ_(H) (400 MHz, DMSO)8.79-8.70 (2H, m), 8.25-8.14 (2H, m), 7.77-7.58 (5H, m), 7.38 (2H, br s)and 5.87 (2H, s). 131 B 22 mp 225.7-225.8° C.; NMR δ_(H) (400 MHz, DMSO)8.33 (1H, d, J 4.5 Hz), 8.13-8.12 (1H, m), 7.92-7.91 (1H, m), 7.30 (2H,br s), 7.15 (1H, d, J 5.0 Hz), 7.07-7.06 (1H, m), 6.86 (1H, dd, J 1.5,3.5 Hz), 5.72 (2H, s), 2.28 (3H, s); Anal. Calcd for C₁₅H₁₃N₇O•0.7H₂O:C, 56.31; H, 4.54, N, 30.65. Found: C, 56.57; H, 4.24; N, 30.33. 132 N10 IR ν_(max) (DR)/cm⁻¹ 3332, 2977, 1694, 1608; NMR δ_(H) (400 MHz,DMSO) 8.41 (1H, d, J 4.5 Hz), 8.14-8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz),7.43 (1H, t, J 6.0 Hz), 7.33 (2H, br s), 7.16 (1H, d, J 4.5 Hz),6.97-6.96 (1H, m), 6.87 (1H, dd, J 2.0, 3.5 Hz), 5.76 (2H, s), 4.10 (2H,d, J 6.0 Hz), 1.31 (9H, s). 133 B 14 mp 209.7-209.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3506, 3311, 3196, 2996, 2951, 1637, 1518 and 1283; NMRδ_(H) (400 MHz, DMSO) 8.15-8.12 (1H, m), 7.91 (1H, dd, J 3.5, 1.0 Hz),7.84 (1H, d, J 8.0 Hz), 7.43 (1H, d, J 1.5 Hz), 7.42-7.35 (2H, s),6.88-6.82 (2H, m), 5.77 (2H, s) and 3.91 (3H, s). 134 B 14 mp240.9-241.1° C. IR ν_(max) (DR)/cm⁻¹ 4010, 3629, 3499, 3313, 3196, 2946,2733, 2447, 1943, 1638, 1528, 1420, 1351, 1222, 1025 and 960. NMR δ_(H)(400 MHz, DMSO) 5.85 (2H, s), 6.84-6.89 (1H, m), 7.36 (2H, s), 7.50 (2H,dt, J 8.5, 2.0 Hz), 7.92 (1H, dd, J 3.5, 1.0 Hz), 8.12-8.14 (1H, m),8.22 (2H, dt, J 9.0, 2.0 Hz). Anal. Calcd for C₁₅H₁₁N₇O₃•0.6H₂O: C,51.75; H, 3.53; N, 28.17. Found: C, 52.08; H, 3.22; N, 27.96. 135 B 18mp 208.6-208.8° C.; IR ν_(max) (DR)/cm⁻¹ 3432, 3304, 3191, 2961, 1616,1500, 1434; NMR δ_(H) (400 MHz, DMSO) 8.14-8.13 (1H, m), 7.93-7.91 (1H,m), 7.67 (1H, t, J 7.5 Hz), 7.35 (2H, br s), 7.19 (1H, d, J 7.5 Hz),6.90-6.86 (2H, m), 5.73 (2H, s), 2.68 (2H, q, J 7.5 Hz), 1.14 (3H, t, J7.5 Hz). 136 B 18 mp 172.7-173.2° C.; NMR δ_(H) (400 MHz, DMSO) 8.42(1H, d, J 5.5 Hz), 8.14 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.39 (2H, brs), 7.11-7.10 (1H, m), 6.97 (1H, d, J 5.5 Hz), 6.87 (1H, dd, J 2.0, 3.5Hz), 5.70 (2H, s), 2.71 (2H, q, J 7.5 Hz), 1.18 (3H, t, J 7.5 Hz). 137 B13 mp 176.3-176.5° C.; IR ν_(max) (DR)/cm⁻¹ 3452, 3326, 3209, 2973,1734, 1611, 1328, 1026 and 774; NMR δ_(H) (400 MHz, DMSO) 8.13 (1H, d, J2.5 Hz), 7.90 (1H, d, J 3.5 Hz), 7.72 (1H, d, J 3.5 Hz), 7.61 (1H, d, J8.5 Hz), 7.34 (2H, br s), 7.19 (1H, t, J 8.0 Hz), 6.86 (1H, dd, J 3.5,2.0 Hz), 6.77 (1H, d, J 4.0 Hz), 6.75 (1H, d, J 7.5 Hz), 6.07 (2H, s)and 1.54 (9H, s). 138 B 26 mp 58.5-62.6° C.; IR ν_(max) (DR)/cm⁻¹ 3430,3315, 3210, 3973, 1718, 1165, 834 and 772; NMR δ_(H) (400 MHz, DMSO)8.13-8.11 (1H, m), 8.03 (1H, d, J 8.0 Hz), 7.89 (1H, d, J 3.5 Hz), 7.73(1H, d, J 4.0 Hz), 7.39 (2H, br s), 7.30 (1H, t, J 8.5 Hz), 7.08 (1H, d,J 7.0 Hz), 6.91 (1H, d, J 4.5 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.90(2H, s) and 1.62 (9H, s). 139 K 85 mp 192.3-193.5° C.; NMR δ_(H) (400MHz, DMSO) 11.27 (1H, br s), 8.12 (1H, d, J 2.5 Hz), 7.90 (1H, d, J 3.5Hz), 7.39-7.33 (2H, m), 7.04 (1H, t, J 8.0 Hz), 6.87-6.83 (2H, m),6.56-6.52 (1H, m) and 5.86 (2H, s). 140 B 20 mp 184.0-185.2° C.; IRν_(max) (DR)/cm⁻¹ 3638, 3462, 3331, 3184, 2976, 1686, 1174, 1026 and756; NMR δ_(H) (400 MHz, DMSO) 8.13 (1H, d, J 1.0 Hz), 7.90 (1H, d, J3.5 Hz), 7.45-7.31 (3H, m), 7.27-7.17 (4H, m), 6.86 (1H, dd, J 3.5, 2.0Hz), 5.64 (2H, s), 4.08 (2H, d, J 6.0 Hz) and 1.37 (9H, s). 141 C 45 mp240.3-240.4° C. IR ν_(max) (DR)/cm⁻¹ 3320, 3198, 2929, 1610, 1505, 1438,1280, 1233, 1028, 956 and 759; NMR δ_(H) (400 MHz, DMSO) 5.85 (2H, s),6.84-6.89 (1H, m), 7.36 (2H, s), 7.50 (2H, dt, J 8.5, 2.0 Hz), 7.92 (1H,dd, J 3.5, 1.0 Hz), 8.12-8.14 (1H, m), 8.22 (2H, dt, J 9.0 Hz). 142 B 14mp 189.0-189.1° C.; IR ν_(max) (DR)/cm⁻¹ 3506, 3304, 3180, 1735, 1609,1167, 1029 and 766; NMR δ_(H) (400 MHz, DMSO) 8.15-8.11 (1H, m), 8.02(1H, d, J 8.5 Hz), 7.91 (1H, d, J 3.5 Hz), 7.68 (1H, d, J 3.5 Hz), 7.53(1H, s), 7.37 (2H, br s), 7.29 (1H, dd, J 8.5, 1.5 Hz), 6.86 (1H, dd, J3.5, 2.0 Hz), 6.70 (1H, d, J 3.5 Hz), 5.75 (2H, s) and 1.61 (9H, s). 143B 18 mp 167.0-167.3° C.; IR ν_(max) (DR)/cm⁻¹ 3650, 3485, 3320, 3194,2978, 1726, 1168, 953 and 756; NMR δ_(H) (400 MHz, DMSO) 9.00 (1H, brs), 8.13 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.57 (1H, t, J 8.0 Hz), 7.39(2H, br s), 7.16 (1H, d, J 11.5 Hz), 7.04 (1H, d, J 8.5 Hz), 6.86 (1H,dd, J 3.5, 2.0 Hz), 5.64 (2H, br s) and 1.44 (9H, s). 144 K 56 mp > 300°C. dec; IR ν_(max) (DR)/cm⁻¹ 2903, 2030, 1606, 1464, 1033, 779 and 589;NMR δ_(H) (400 MHz, DMSO) 8.30 (2H, br s), 8.14 (1H, s), 7.92 (1H, d, J3.5 Hz), 7.46 (2H, d, J 8.0 Hz), 7.32 (2H, d, J 8.0 Hz), 6.92-6.84 (1H,m), 5.69 (2H, s) and 4.04-3.96 (2H, m). 145 H 30 IR ν_(max) (DR)/cm⁻¹3511, 3292, 3164, 2971, 1609, 1525, 1437, 1354 and 1239; NMR δ_(H) (400MHz, DMSO) 8.19 (2H, m), 7.90 (1H, d, J 3.5 Hz), 7.72-7.64 (2H, m), 7.36(2H, br s), 6.53 (1H, d, J 3.5 Hz), 5.83 (2H, s), 2.80 (2H, q, J 7.5 Hz)and 1.27 (3H, t, J 7.5 Hz). 146 B 35 mp 180.0-180.5° C.; IR ν_(max)(DR)/cm⁻¹ 3325, 3206, 2976, 1734, 1604, 1341, 1024 and 768; NMR δ_(H)(400 MHz, DMSO) 7.92 (1H, d, J 3.0 Hz), 7.84 (1H, s), 7.67 (1H, d, J 4.0Hz), 7.62 (1H, d, J 8.0 Hz), 7.37 (2H, br s), 7.26 (1H, d, J 8.0 Hz),6.87 (1H, dd, J 3.5, 1.5 Hz), 6.70 (1H, d, J 3.5 Hz), 5.80 (2H, s) and1.51 (9H, s). 147 K 57 mp > 200° C. dec; IR ν_(max) (DR)/cm⁻¹ 2816,2004, 1660, 1507, 1427, 1277, 1030, 746 and 524; NMR δ_(H) (400 MHz,DMSO) 8.15-8.12 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.14 (1H, d, J 12.0Hz), 7.06-6.94 (2H, m), 6.86 (1H, dd, J 3.5, 2.0 Hz) and 5.57 (2H, s).148 B 43 Mp 259.8-259.9° C. IR ν_(max) (DR)/cm⁻¹ 3382, 3214, 2986, 2731,2090, 1767, 1730, 1606, 1487, 1372, 1275, 1137, 1029, 873 and 771; NMRδ_(H) (400 MHz, DMSO) 1.49 (9H, s), 5.63 (2H, s), 6.85-6.86 (1H, m),7.20-7.27 (2H, m), 7.40 (2H, s), 7.87 (1H, d, J 3.0 Hz), 8.11-8.14 (1H,m). 149 K 96 IR ν_(max) (Nujol)/cm⁻¹ 3375, 3061, 1653, 1509 and 1474;NMR δ_(H) (400 MHz, DMSO) 11.15-10.13 (1H, s), 8.43-7.36 (3H, s),8.14-8.12 (1H, m), 7.89 (1H, dd, J 3.5, 1.0 Hz), 6.87-6.84 (1H, m),6.59-6.51 (2H, m) and 5.51 (2H, s). 150 C 37 IR ν_(max) (DR)/cm⁻¹ 4043,3461, 3312, 3198, 2970, 2748, 2438, 1923, 1650, 1514, 1497 and 1324; NMRδ_(H) (400 MHz, DMSO) 7.9 (1H, d, J 3.5 Hz), 7.31 (2H, br s), 6.97 (1H,t, J 8.0 Hz), 6.53 (1H, d, J 3.5 Hz), 6.45 (1H, dd, J 1.5, 8.0 Hz), 6.40(1H, d, J 7.5 Hz), 6.34 (1H, t, J 1.7 Hz), 5.48 (2H, s), 5.12 (2H, s),2.80 (2H, q, J 7.5 Hz) and 1.27 (3H, t, J 7.5 Hz). 151 C 48 mp251.2-251.5° C.; IR ν_(max) (DR)/cm⁻¹ 3449, 3365, 3314, 3196, 2954,2742, 1731, 1642, 1598, 1556, 1463 and 1407; NMR δ_(H) (400 MHz, DMSO)8.76-8.72 (2H, m), 7.67-7.62 (3H, m), 7.36 (2H, br s), 6.97 (1H, t, J8.0 Hz), 6.46 (1H, dd, J 1.5, 8.0 Hz), 6.43 (1H, d, J 7.5 Hz), 6.36 (1H,t, J 1.7 Hz), 5.52 (2H, s) and 5.13 (2H, s). 152 AF 86 mp 298.9-299.0°C.; IR ν_(max) (DR)/cm⁻¹ 3422, 3321, 3105, 3942, 1601, 1351, 1219, 1019and 762; NMR δ_(H) (400 MHz, DMSO) 11.09 (1H, br s), 8.13 (1H, s), 7.91(1H, d, J 3.0 Hz), 7.51 (1H, d, J 8.5 Hz), 7.43-7.31 (3H, m), 7.28 (1H,s), 7.00 (1H, d, J 8.0 Hz), 6.89-6.83 (1H, m), 6.39 (1H, s) and 5.73(2H, br s). 153 AF 75 mp 226.8-227.4° C.; IR ν_(max) (DR)/cm⁻¹ 3475,3320, 2739, 1645, 1506, 1223, 1008 and 778; NMR δ_(H) (400 MHz, DMSO)11.14 (1H, br s), 8.14-8.10 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.50 (1H,s), 7.40-7.31 (4H, m), 7.09 (1H, dd, J 8.0, 1.5 Hz), 6.85 (1H, dd, J3.5, 1.5 Hz), 6.43-6.38 (1H, m) and 5.70 (2H, s). 154 AF 77 mp295.3-295.5° C.; IR ν_(max) (DR)/cm⁻¹ 3215, 1610, 1005, 758, 650 and565; NMR δ_(H) (400 MHz, DMSO) 11.36 (1H, br s), 8.15-8.11 (1H, m), 7.91(1H, d, J 3.5 Hz), 7.51 (1H, d, J 8.0 Hz), 7.46 (1H, t, J 2.5 Hz), 7.43(2H, br s), 6.92 (1H, t, J 7.5 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.71(1H, d, J 7.0 Hz), 6.53-6.49 (1H, m) and 5.93 (2H, s). 155 B 35 mp258.6-258.7° C.; IR ν_(max) (Nujol)/cm⁻¹ 3386, 3206, 1646, 1607 and1481; NMR δ_(H) (400 MHz, DMSO) 8.33 (1H, dd, J 9.0, 4.5 Hz), 8.15 (1H,s), 7.92 (1H, d, J 3.5 Hz), 7.55-7.47 (1H, m), 7.47-7.35 (2H, s),6.93-6.85 (2H, m) and 6.03 (2H, s). 156 AG 99 mp 274.2-274.3° C.; IRν_(max) (Nujol)/cm⁻¹ 3482, 3305, 3197, 2963, 1606, 1499 and 1420; NMRδ_(H) (400 MHz, DMSO) 8.12 (1H, s), 7.87 (1H, d, J 3.0 Hz), 7.37 (2H,s), 6.86-6.77 (3H, m), 5.55 (2H, s) and 3.79 (3H, s); Anal. Calcd forC₁₆H₁₂N₆O₂F₂•0.5H₂O: C, 52.32; H, 3.57, N, 22.88. Found: C, 52.62; H,3.31; N, 22.72. 157 B 24 mp 204.2-204.4° C.; NMR δ_(H) (400 MHz, DMSO)1.41 (9H, s), 4.37, (2H, d, J 6.0 Hz), 5.72 (2H, s), 6.83 (1H, d, J 6.0Hz), 6.85-6.88 (1H, d, J 7.5 Hz), 7.14-7.22 (1H, m), 7.30 (2H, d, J 4.0Hz), 7.36 (2H, s), 7.48 (1H, t, J 6.0 Hz), 7.91 (1H, d, J 3.5 Hz),8.12-8.14 (1H, m). Anal. Calcd for C₂₁H₂₃N₇O₃: C, 59.85; H, 5.50; N,23.25. Found: C, 59.69; H, 5.54; N, 22.74. 158 AZ mp > 300° C. dec; IRν_(max) (DR)/cm⁻¹ 3212, 1607, 1438, 1212, 1029 and 770; NMR δ_(H) (400MHz, DMSO) 15.74 (1H, br s), 8.13 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.80(2H, br s), 7.54-7.30 (3H, s), 6.86 (1H, dd, J 4.0, 2.0 Hz) and 5.85(2H, s). 159 B 16 Mp 235.9-237.8° C.; NMR δ_(H) (400 MHz, DMSO)8.15-8.13 (1H, m), 7.93-7.91 (1H, d, J 3.5 Hz), 7.84-7.82 (1H, d, J 2.5Hz), 7.80-7.76 (1H, dd, J 2.5, 8.5 Hz), 7.43-7.37 (2H, s) 7.04-7.00 (1H,d, J 8.5 Hz), 6.89-6.86 (1H, dd, J 2.0, 3.5 Hz), 5.71-5.69 (2H s), and3.99-3.97 (3H s). 160 B 28 mp 277.4-277.9° C.; NMR δ_(H) (400 MHz, DMSO)9.93 (1H, s), 8.15-8.12 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.55 (1H, d, J8.0 Hz), 7.38 (2H, s), 7.34 (1H, s), 7.27 (1H, t, J 8.0 Hz), 6.96 (1H,d, J 7.5 Hz), 6.88-6.85 (1H, m), 5.63 (2H, s) and 1.99 (3H, s). 161 K100 mp > 250° C. dec; IR ν_(max) (DR)/cm⁻¹ 3035, 1968, 1654, 1464, 1354,1247, 1032 and 746; NMR δ_(H) (400 MHz, DMSO) 4.39 (2H, q, J 5.5 Hz),5.81 (2H, s), 6.84-6.89 (1H, m), 7.13 (1H, d, J 7.5 Hz), 7.31-7.46 (3H,m), 7.55 (1H, d, J 7.5 Hz), 7.90 (1H, d, J 3.5 Hz), 8.12-8.16 (1H, m),8.44 (3H, s). Anal. Calcd for C₁₆H₁₅N₇O•2HCl•1.5H₂O: C, 45.62; H, 4.79;N, 23.27. Found: C, 45.63; H, 4.71; N, 23.14. 162 B 14 mp 195.1-195.2°C.; IR ν_(max) (DR)/cm⁻¹ 3490, 3375, 3310, 3199, 2895, 1734, 1609, 1507,1421, 1228, 1026, 1001 and 760; NMR δ_(H) (400 MHz, DMSO) 2.86 (6H, s),5.58 (2H, s), 6.48 (1H, d, J 7.5 Hz), 6.64 (1H, dd, J 8.0, 2.0 Hz),6.72-6.75 (1H, m), 6.84-6.87 (1H, m), 7.12 (1H, t, J 7.5 Hz), 7.35 (2H,s), 7.90 (1H, d, J 3.5 Hz) and 8.10-8.14 (1H, m). 163 B 20 IR ν_(max)(DR)/cm⁻¹ 3489, 3324, 3199, 2560, 1605, 1235, 1121, 1048 and 762; NMRδ_(H) (400 MHz, DMSO) 8.12 (1H, d, J 2.5 Hz), 7.90 (1H, d, J 3.5 Hz),7.44-7.32 (4H, m), 7.16 (2H, d, J 9.0 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz)and 5.67 (2H, s). 164 B 16 mp 120.1-121.0° C.; IR ν_(max) (DR)/cm⁻¹3318, 1772, 1709, 1607, 1462, 1395; NMR δ_(H) (400 MHz, DMSO) 8.15-8.14(1H, m), 7.81 (1H, d, J 3.5 Hz), 7.77 (1H, t, J 8.0 Hz), 7.71-7.65 (4H,m), 7.33 (1H, d, J 8.0 Hz), 7.21 (2H, br s), 7.12 (1H, d, J 8.0 Hz),6.88 (1H, dd, J 1.5, 3.5 Hz), 5.68 (2H, s), 4.80 (2H, s). 165 C 60 mp259.7-259.8° C.; IR ν_(max) (DR)/cm⁻¹ 3457, 3315, 3183, 2959, 2747,1734, 1653, 1608, 1518, 1441, 1420 and 1386; NMR δ_(H) (400 MHz, DMSO)8.12 (1H, d, J 1.0 Hz), 7.90 (1H, d, J 3.5 Hz), 7.35 (2H, br s), 6.93(1H, dd, J 8.0, 11.5 Hz), 6.86 (1H, dd, 1.5, J 3.5 Hz), 6.58 (1H, dd, J2.0, J 8.5 Hz) 6.47-6.39 (1H, m), 5.49 (2H, s) and 5.19 (2H, s). 166 B10 mp 210.3-211.2° C.; NMR δ_(H) (400 MHz, DMSO) 8.15-8.10 (1H, m), 7.89(1H, d, J 4.5 Hz), 7.35 (2H, br s), 7.18 (1H, s), 7.08 (1H, d, J 8.0Hz), 6.85 (1H, dd, J 3.5, 1.5 Hz), 6.72 (1H, d, J 8.0 Hz), 5.55 (1H, s),4.49 (2H, t, J 8.5 Hz) and 3.13 (2H, t, J 8.5 Hz). 167 B 11 IR ν_(max)(Nujol)/cm⁻¹ 3486, 3319, and 1606; NMR δ_(H) (400 MHz, DMSO) 8.15-8.10(1H, m), 7.92-7.87 (1H, d, J 3.5 Hz), 7.64-7.56 (1H, m), 7.54-7.47 (1H,m), 7.46-7.35 (2H, s), 7.32-7.22 (1H, t, J 9.5 Hz), 6.88-6.84 (1H, dd, J2.0, 3.5 Hz), and 5.71-5.65 (2H s); Anal. Calcd for C₁₅H₁₀N₆OFBr•0.5H₂O:C, 45.25; H, 2.78; N, 21.11. Found: C, 45.10; H, 2.48; N, 20.69. 168 B12 Mp 204.0-204.2° C.; IR ν_(max) (Nujol)/cm⁻¹ 3343 and 3208; NMR δ_(H)(400 MHz, DMSO) 8.14-8.12 (1H, m), 7.91-7.89 (1H, dd, J 1.0, 3.5 Hz),7.62-7.53 (1H, m), 7.45-7.37 (2H, s), 7.05-6.97 (1H, m), 6.88-6.85 (1H,dd, J 2.0, 3.5 Hz), and 5.76-5.74 (2H, s). 169 B 11 IR ν_(max)(Nujol)/cm⁻¹ 3490 and 3321; NMR δ_(H) (400 MHz, DMSO) 8.15-8.13 (1H, m),7.91-7.89 (1H, d, J 3.5 Hz), 7.78-7.72 (1H, m), 7.67-7.63 (1H, dd, J2.0, 7.0 Hz), 7.46-7.38 (2H, s), 7.15-7.08 (1H, dd, J 9.0, 10.0 Hz)6.88-6.85 (1H, dd, J 2.0, 3.5 Hz), and 5.67-5.64 (2H, s). 170 B 18 IRν_(max) (Nujol)/cm⁻¹ 3495 and 3304; NMR δ_(H) (400 MHz, DMSO) 8.14-8.12(1H, m), 7.90-7.88 (1H, dd, J 1.0, 3.5 Hz), 7.64-7.62 (1H, dd, J 1.0,2.0 Hz), 7.43-7.37 (2H, s), 6.87-6.84 (1H, dd, J 1.5, 3.5 Hz), 6.51-6.48(1H, dd, J 1.0, 3.5 Hz), 6.46-6.44 (1H, dd, J 2.0, 3.5 Hz) and 5.67-5.65(2H, s). 171 C 59 mp 219.3° C.; IR ν_(max) (Nujol)/cm⁻¹ 3508, 3421,3307, 3190, 2949, 1609 and 1506; NMR δ_(H) (400 MHz, DMSO) 8.14 (1H, s),7.91 (1H, d, J 3.5 Hz), 7.43 (2H, s), 6.92-6.85 (2H, m), 6.72 (1H, dd, J8.5, 5.0 Hz), 6.52 (1H, dd, J 9.5, 3.0 Hz), 5.47 (2H, s) and 5.19 (2H,s). 172 B 18 IR ν_(max) (Nujol)/cm⁻¹ 3490, 3304, 3182, 2986, 1779, 1762,1603, 1345 and 1231; NMR δ_(H) (400 MHz, DMSO) 8.16 (1H, d, J 8.5 Hz),8.15-8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.46 (1H, d, J 2.0 Hz),7.45-7.36 (2H, s), 7.32 (1H, dd, J 8.5, 1.5 Hz), 6.88-6.86 (1H, m), 5.84(2H, s) and 1.47 (9H, s). 173 C 78 mp 239.6-239.8° C.; IR ν_(max)(Nujol)/cm⁻¹ 3323, 2936, 2733, 1772, 1734, 1609, 1508 and 1282; NMRδ_(H) (400 MHz, DMSO) 9.07 (1H, s), 8.13-8.11 (1H, m), 7.89 (1H, d, J3.5 Hz), 7.34 (2H, s), 6.87-6.84 (1H, m), 6.59-6.50 (3H, m), 5.41 (2H,s) and 4.57 (2H, s). 174 K 81 mp > 200° C. dec; IR ν_(max) (DR)/cm⁻¹3144, 2570, 2004, 1654, 1458, 1369, 1280, 1037 and 760; NMR δ_(H) (400MHz, DMSO) 7.87 (1H, d, J 3.5 Hz), 7.13 (1H, d, J 11.5 Hz), 7.05-6.91(2H, m), 6.51 (1H, dd, J 3.5, 1.0 Hz), 5.55 (2H, s) and 2.45 (3H, s).175 C 17 mp 279.3-281.3° C.; IR ν_(max) (DR)/cm⁻¹ 3462, 3202, 2952,1653, 1510, 1462, 1416, 1342, 1293 and 1261; NMR δ_(H) (400 MHz,DMSO)13.52 (1H, br s), 7.97 (1H, br s), 7.31 (1H, s), 7.25 (2H, br s),6.96 (1H, t, J 7.5 Hz), 6.46 (1H, dd, J 1.0, 8.0 Hz), 6.42 (1H, d, J7.0), 6.34 (1H, s), 5.50 (2H, s) and 5.13 (2H, s). 176 K 51 IR ν_(max)(Nujol)/cm⁻¹ 3651, 3488, 3317, 1637, 1507 and 1331; NMR δ_(H) (400 MHz,DMSO) 11.04 (1H, s), 8.15-8.13 (1H, m), 7.92 (1H, dd, J 3.5, 1.0 Hz),7.87 (1H, d, J 8.5 Hz), 7.41 (2H, s), 6.88-6.86 (1H, m), 6.85-6.81 (2H,m) and 5.72 (2H, s); Anal. Calcd for C₁₅H₁₁N₇O₄•1.0H₂O: C, 48.52; H,3.53, N, 26.24. Found: C, 48.68; H, 3.20; N, 26.24. 177 AL 65 mp245.9-247.0° C.; IR ν_(max) (DR)/cm⁻¹ 3284, 3194, 1654, 1609, 1523; NMRδ_(H) (400 MHz, DMSO) 8.41 (1H, t, J 6.0 Hz), 8.14-8.13 (1H, m), 7.92(1H, dd, J 1.0, 3.5 Hz), 7.73 (1H, t, J 7.5 Hz), 7.37 (2H, br s), 7.21(1H, d, J 7.5 Hz), 6.93 (1H, d, J 7.5 Hz), 6.88-6.86 (1H, m), 5.74 (2H,s), 4.28 (2H, d, J 6.0 Hz), 1.88 (3H, s); Anal. Calcd forC₁₇H₁₆N₈O₂•0.5H₂O•0.1C₃H₇NO: C, 54.58; H, 4.69, N, 29.80. Found: C,54.90; H, 4.43; N, 29.46. 178 R 20 mp 216.7-218.4° C.; IR ν_(max)(DR)/cm⁻¹ 3854, 3143, 2569, 2004, 1654, 1518, 1437, 1279, 1207, 1037 and868; NMR δ_(H) (400 MHz, DMSO) 1.90 (3H, s), 4.48 (2H, d, J 6.0 Hz),5.73 (2H, s), 6.82-6.89 (2H, m), 7.15-7.23 (1H, m), 7.25-7.46 (4H, m),7.91 (1H, d, J 3.5 Hz), 8.12-8.15 (1H, m), 8.39 (1H, t, J 5.5 Hz). 179 B11 Mp 215.8-216.9° C.; IR ν_(max) (Nujol)/cm⁻¹ 3482 and 3305; NMR δ_(H)(400 MHz, DMSO) 8.13-8.11 (1H, m), 7.91-7.89 (1H, d, J 3.5 Hz),7.55-7.52 (1H, dd, J 3.0, 5.0 Hz), 7.42-7.40 (1H, m), 7.39-7.34 (2H, s),7.11-7.08 (1H, dd, J 1.5, 5.0 Hz), 6.87-6.85 (1H, dd J 1.5, 3.5 Hz) and5.66-5.64 (2H, s); Anal. Calcd for C₁₃H₁₀N₆OS: C, 52.34; H, 3.38, N,28.16. Found: C, 52.53; H, 3.57; N, 28.22. 180 C 25 mp 278.4-279.9° C.;IR ν_(max) (DR)/cm⁻¹ 3468, 3184, 2967, 1735, 1604, 1436, 1322, 1234 and1204; NMR δ_(H) (400 MHz, DMSO) 7.87 (1H, d, J 3.0 Hz), 7.30 (2H, br s),6.80 (1H, t, J 8.0 Hz), 6.58 (1H, dd, J 1.0, 8.0 Hz), 6.51 (1H, dd, J3.0, 1.0 Hz), 6.11 (1H, d, J 7.0 Hz), 5.54 (2H, s), 4.93 (2H, br s),2.45 (3H, s) and 2.1 (3H, s). 181 B 12 IR ν_(max) (Nujol)/cm⁻¹ 3501 and3316; NMR δ_(H) (400 MHz, DMSO) 8.13-8.11 (1H, m), 7.90-7.87 (1H, dd, J1.0, 3.5 Hz), 7.43-7.32 (2H, s), 7.40-7.37 (1H, d, J 5.0 Hz), 6.90-6.87(1H, d, J 5.0 Hz), 6.86-6.84 (1H, dd, J 2.0, 3.5 Hz), 5.73-5.72 (2H, s),and 2.37-2.35 (3H, s). 182 AM 30 mp 92.3-92.7° C.; IR ν_(max) (DR)/cm⁻¹3124, 3073, 2926, 1609, 1520, 1411; NMR δ_(H) (400 MHz, DMSO) 8.18-8.17(1H, m), 7.93 (1H, d, J 3.0 Hz), 7.80 (1H, t, J 7.5 Hz), 7.37 (1H, d, J7.5 Hz), 7.19 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5 Hz), 5.94-5.75(3H, m), 5.78 (2H, s), 5.28-5.07 (6H, m), 4.48 (2H, s), 4.43-4.12 (4H,m), 4.02-3.99 (2H, m); Anal. Calcd for C₂₄H₂₅N₇O₂: C, 65.00; H, 5.68, N,22.10. Found: C, 65.23; H, 5.80; N, 21.60. 183 B 27 mp 152.0-153.5° C.;IR ν_(max) (DR)/cm⁻¹ 3515, 3300, 3183, 2934, 2822, 1631, 1450, 1434; NMRδ_(H) (400 MHz, DMSO) 7.89 (1H, d, J 3.0 Hz), 7.79 (1H, t, J 7.5 Hz),7.33 (2H, br s), 7.34 (1H, d, J 7.5 Hz), 7.02 (1H, d, J 7.5 Hz),6.53-6.51 (1H, m), 5.74 (2H, s), 4.43 (2H, s), 2.46 (3H, s), 3.33 (3H,s); Anal. Calcd for C₁₇H₁₇N₇O₂: C, 58.11; H, 4.88, N, 27.89. Found: C,57.75; H, 4.85; N, 27.59. 184 C 76 mp 219.7-220.4° C. IR ν_(max)(DR)/cm⁻¹ 3450, 3312, 2920, 2728, 1737, 1638, 1438, 1354, 1326, 1291and1234; NMR δ_(H) (400 MHz, DMSO) 7.85 (1H, d, J 3.0 Hz), 7.30 (2H, br s),7.01 (2H, d, J 8.5 Hz), 6.52-6.47 (3H, m), 5.41 (2H, s), 5.12 (2H, s)and 2.44 (3H, s). 185 B 15 mp 155.6-157.1° C.; IR ν_(max) (DR)/cm⁻¹3332, 3197, 2857, 1655, 1605, 1525, 1420; NMR δ_(H) (400 MHz, DMSO)8.14-8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.79 (1H, t, J 7.5 Hz), 7.37(1H, d, J 7.5 Hz), 7.36 (2H, br s), 7.05 (1H, d, J 7.5 Hz), 6.88-6.86(1H, m), 5.98-5.86 (1H, m), 5.76 (2H, s), 5.29-5.24 (1H, m), 5.17-5.13(1H, m), 4.48 (2H, s), 4.06-4.00 (2H, m); Anal. Calcd for C₁₈H₁₇N₇O₂: C,59.50; H, 4.72, N, 26.97. Found: C, 59.39; H, 4.70; N, 26.99. 186 B 23mp 149.0-149.3° C.; IR ν_(max) (DR)/cm⁻¹ 3514, 3295, 3168, 2861, 1634,1502, 1435; NMR δ_(H) (400 MHz, DMSO) 7.88 (1H, d, J 3.5 Hz), 7.79 (1H,t, J 7.5 Hz), 7.37 (1H, d, J 7.5 Hz), 7.33 (2H, br s), 7.04 (1H, d, J7.5 Hz), 6.52-6.51 (1H, m), 5.96-5.86 (1H, m), 5.74 (2H, s), 5.30-5.24(1H, m), 5.17-5.13 (1H, m), 4.49 (2H, s), 4.06-4.00 (2H, m), 2.46 (3H,s); Anal. Calcd for C₁₉H₁₉N₇O₂•0.2 H₂O: C, 59.90; H, 5.13, N, 25.73.Found: C, 59.71; H, 5.02; N, 25.64. 187 B 20 mp 191.7-191.9° C.; IRν_(max) (Nujol)/cm⁻¹ 3501, 3307, 3189, 2974, 1611, 1527 and 1338; NMRδ_(H) (400 MHz, DMSO) 8.12-8.15 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.76(1H, d, J 8.5 Hz), 7.67 (1H, d, J 2.0 Hz), 7.44-7.36 (2H, s), 7.16 (1H,dd, J 8.5, 2.0 Hz), 6.87-6.85 (1H, m), 5.78 (2H, s), 3.22 (1H, quin, J6.5 Hz) and 1.22 (6H, d, J 6.5 Hz). 188 B 32 mp 228.9-229.9° C.; IRν_(max) (DR)/cm⁻¹ 3461, 3317, 3195, 1606, 1504, 1320, 1026 and 818; NMRδ_(H) (400 MHz, DMSO) 8.16-8.14 (1H, m), 7.98 (1H, d, J 8.0 Hz), 7.94(1H, d, J 3.5, 1.0 Hz), 7.91 (1H, d, J 8.0 Hz), 7.78-7.73 (1H, m),7.64-7.58 (1H, m), 7.36 (1H, d, J 8.5 Hz), 7.36 (2H, br s), 6.88 (1H,dd, J 3.5, 1.5 Hz) and 5.98 (2H, s). 189 K 23 NMR δ_(H) (400 MHz, DMSO)8.14-8.12 (1H, m), 7.92-7.89 (1H, dd, J 1.0, 3.5 Hz), 7.35-7.31 (2H, d,J 8.5 Hz), 7.28-7.16 (2H, s), 6.88-6.85 (1H, dd, J 1.5, 3.5 Hz),5.66-5.64 (2H, s), and 2.82-2.80 (3H, s); M/Z 322 (M + H)⁺. 190 B 37 mp290.2-290.3° C.; IR ν_(max) (DR)/cm⁻¹ 3491, 3338, 3205, 3128, 2936,1710, 1616, 1490, 1458; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m),7.93 (1H, t, J 7.5 Hz), 7.90 (1H, dd, J 1.0, 3.5 Hz), 7.84 (1H, d, J 7.5Hz), 7.56 (1H, d, J 7.5 Hz), 7.34 (2H, br s), 6.86 (1H, dd, J 2.0, 3.5Hz), 6.69 (1H, q, J 7.5 Hz), 2.48 (3H, s), 1.98 (3H, d, J 7.5 Hz); Anal.Calcd for C₁₇H₁₅N₇O₂: C, 58.45; H, 4.33, N, 28.05. Found: C, 58.26; H,4.42; N, 27.67. 191 C 16 mp 186.1-189.1° C.; IR ν_(max) (DR)/cm⁻¹ 3458,1598, 1509, 1460, 1329, 1267 and 1220; NMR δ_(H) (400 MHz, DMSO) 11.73(1H, s), 7.59 (1H, s), 7.17 (1H, s), 6.97 (1H, t, J 7.8 Hz), 6.95-6.83(2H, br s), 6.45 (1H, dd, J 1.5, J 8.0 Hz), 6.40 (1H, d, J 8.0 Hz),6.38-6.31 (1H, m), 5.47 (2H, s) and 5.13 (2H, s). 192 Q 2 NMR δ_(H) (400MHz, CD₃OD) 8.84 (1H, d, J 4.5 Hz), 8.77 (1H, d, J 8.0 Hz), 8.33 (1H, t,J 1.7 Hz), 8.2 (1H, dd, J 2.0, 8.0 Hz), 8.06 (1H, td, J 7.8, 2.0 Hz),7.81 (1H, d, J 7.5 Hz), 7.65-7.58 (2H, m) and 5.88 (2H, s); M/Z 349 (M +H)⁺; Retention time 1.77 min. 193 B 6 mp 253.6-254.0° C.; IR ν_(max)(DR)/cm⁻¹ 3320, 1611, 1414, 1315, 1255, 1026 and 767; NMR δ_(H) (400MHz, DMSO) 2.01 (3H, s), 5.59 (2H, s), 6.84-6.88 (1H, m), 7.22 (2H, d, J8.5 Hz), 7.36 (2H, s), 7.54 (2H, d, J 8.5 Hz) 7.90 (1H, d, J 3.5 Hz),8.11-8.14 (1H, m), 9.97 (1H, s). 194 B 36 mp 136.5-137.6° C.; IR ν_(max)(Nujol)/cm⁻¹ 3489, 3311, 3195, 2954, 1774 and 1613; NMR δ_(H) (400 MHz,DMSO) 8.24 (1H, s), 8.04 (1H, d, J 2.0 Hz), 8.00 (1H, d, J 3.5 Hz), 7.96(1H, dd, J 8.5, 2.0 Hz), 7.52-7.44 (2H, s), 7.40 (1H, d, J 8.5 Hz),6.99-6.95 (1H, m), 5.83 (2H, s), 5.54 (2H, s), 3.66 (2H, t, J 8.0 Hz),0.93 (2H, t, J 8.0 Hz) and 0.00 (9H, s); Anal. Calcd forC₂₁H₂₅N₇O₅Si•0.1H₂O: C, 51.97; H, 5.23, N, 20.20. Found: C, 51.97; H,5.19; N, 19.86. 195 B 12 IR ν_(max) (Nujol)/cm⁻¹ 3652, 3506, 3307, 3196,2990, 2878, 1633, 1521 and 1344; NMR δ_(H) (400 MHz, DMSO) 8.14 (1H, s),7.94-7.88 (2H, m), 7.46 (1H, s), 7.40 (2H, s), 7.23 (1H, dd, J 8.5, 2.0Hz), 6.88-6.85 (1H, m), 5.78 (2H, s), 2.80 (2H, q, 7.5 Hz) and 1.17 (3H,t, J 7.5 Hz); Anal. Calcd for C₁₇H₁₅N₇O₃•0.25H₂O: C, 55.21; H, 4.22, N,26.51. Found: C, 55.47; H, 4.12; N, 26.25. 196 B 23 mp 178.4-179.0° C.;IR ν_(max) (Nujol)/cm⁻¹ 3469 and 3311; NMR δ_(H) (400 MHz, DMSO)8.13-8.11 (1H, m), 7.90-7.88 (1H, dd, J 1.0, 3.5 Hz), 7.37-7.32 (2H, s),7.32-7.29 (1H, dd, J 1.5, 5.5 Hz), 6.92-6.89 (1H, dd, J 3.5, 5.5 Hz),6.87-6.84 (2H, m), 4.70-4.64 (2H, t, J 7.0 Hz), and 3.53-3.48 (2H, t, J7.0 Hz); Anal. Calcd for C₁₄H₁₂N₆OS: C, 53.84; H, 3.87; N, 26.89. Found:C, 53.98; H, 3.87; N, 26.50. 197 B 22 mp 188.3-188.5° C.; IR ν_(max)(DR)/cm⁻¹ 3324, 3189, 2964, 1649, 1513; NMR δ_(H) (400 MHz, DMSO)8.14-8.13 (1H, m), 7.93 (1H, d, J 3.5 Hz), 7.67 (1H, t, J 7.5 Hz), 7.34(2H, br s), 7.20 (1H, d, J 7.5 Hz), 6.89 (1H, d, J 7.5 Hz), 6.87-6.86(1H, m), 5.75 (2H, s), 2.93 (1H, sept, J 7.0 Hz), 1.12 (6H, d, J 7.0Hz); Anal. Calcd for C₁₇H₁₇N₇O: C, 60.88; H, 5.11, N, 29.22. Found: C,61.03; H, 5.13; N, 28.95. 198 B 27 IR ν_(max) (DR)/cm⁻¹ 3466, 3312,3187, 2958, 2850, 1639, 1511, 1221, 1047, 756 and 599; NMR δ_(H) (400MHz, DMSO) 8.13 (1H, s), 8.09 (1H, s), 7.91 (1H, d, J 3.0 Hz), 7.72 (1H,d, J 8.5 Hz), 7.68 (1H, s), 7.42 (1H, d, J 8.5 Hz), 7.37 (2H, br s),6.88-6.83 (1H, m), 5.82 (1H, d, J 9.5 Hz), 5.77 (2H, s), 3.90-3.80 (1H,m), 3.77-3.64 (1H, m), 2.45-2.30 (1H, m), 2.10-1.88 (2H, m), 1.80-1.63(1H, m), 1.62-1.49 (2H, m). 199 B 7 mp 226.5-227.9° C.; IR ν_(max)(DR)/cm⁻¹ 3466, 3316, 3182, 2962, 1645, 1606, 1546, 1514, 1473; NMRδ_(H) (400 MHz, DMSO) 8.14-8.13 (1H, m), 7.92 (1H, d, J 3.0 Hz), 7.33(2H, br s), 7.07-7.06 (1H, m), 6.88-6.86 (2H, m), 5.71 (2H, s), 2.88(1H, sept, J 7.0 Hz), 2.82 (1H, sept, J 7.0 Hz), 1.14 (6H, d, J 7.0 Hz),1.09 (6H, d, J 7.0 Hz). 200 K 99 mp > 300° C. dec; IR ν_(max) (DR)/cm⁻¹3100, 1662, 1465, 1281, 1032, 782 and 592; NMR δ_(H) (400 MHz, DMSO)8.16-8.13 (1H, m), 8.07 (1H, s), 7.92 (1H, d, J 3.5 Hz), 7.68 (1H, s),7.54 (1H, d, J 8.5 Hz), 7.35 (1H, dd, 8.5, 1.5 Hz), 6.87 (1H, dd, J 3.5,2.0 Hz) and 5.76 (1H, s) 201 K 99 IR ν_(max) (Nujol)/cm⁻¹ 2999, 1656,1530 and 1461; NMR δ_(H) (400 MHz, DMSO) 11.10 (1H, s), 8.14 (1H, d, J1.0 Hz), 7.92 (1H, d, J 3.5 Hz), 7.72 (1H, d, J 2.5 Hz), 7.61 (1H, dd, J8.5, 2.5 Hz), 7.0 (1H, d, J 8.5 Hz), 6.86-6.88 (1H, m), 5.67 (2H, s) and5.11-5.16 (3H, s). 202 B 32 mp 210.5-211.6° C.; IR ν_(max) (FILM)/cm⁻¹3352, 3204, 3001, 1659, 1569, 1510, 1440; NMR δ_(H) (400 MHz, DMSO) 8.14(1H, m), 7.93 (1H, d, J 3.5 Hz), 7.76 (1H, t, J 7.5 Hz), 7.43 (1H, d, J7.5 Hz), 7.36 (2H, br s), 7.03 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 2.0,3.5 Hz), 6.75 (1H, dd, J 10.5, 17.5 Hz), 6.09 (1H, dd, J 2.0, 17.5 Hz),5.78 (2H, s), 5.43 (1H, dd, J 1.5, 10.5 Hz); Anal. Calcd for C₁₆H₁₃N₇O:C, 60.18; H, 4.10, N, 30.69. Found: C, 60.14; H, 4.20; N, 30.39. 203 AS12 IR ν_(max) (Nujol)/cm⁻¹ 3514, 3298 and 1761; NMR δ_(H) (400 MHz,DMSO) 8.16-8.15 (1H, m), 7.89-7.86 (1H, dd, J 1.0, 3.5 Hz), 7.80-7.40(2H, s), 6.89-6.86 (1H, dd, J 1.5, 3.5 Hz), and 1.66-1.64 (9H, s). 204 B16 mp 143.6-144.5° C.; IR ν_(max) (DR)/cm⁻¹ 3644, 3315, 3195, 2978,1743, 1608, 1163, 1086 and 746; NMR δ_(H) (400 MHz, DMSO) 8.14-8.10 (1H,m), 8.05 (1H, d, J 8.0 Hz), 7.88 (1H, d, J 3.5 Hz), 7.81 (1H, s), 7.66(1H, d, J 7.5 Hz), 7.42 (2H, br s), 7.34 (1H, t, J 8.0 Hz), 7.23 (1H, t,J 8.0 Hz), 6.85 (1H, dd, J 3.5, 2.0 Hz), 5.78 (2H, s) and 1.63 (9H, s)205 B 19 IR ν_(max) (DR)/cm⁻¹ 3431, 3325, 3217, 1646, 1504, 1431; NMRδ_(H) (400 MHz, DMSO) 9.87-9.86 (1H, m), 8.14 (1H, m), 8.05 (1H, t, J8.0 Hz), 7.94-7.92 (1H, m), 7.88 (1H, d, J 8.0 Hz), 7.52 (1H, d, J 8.0Hz), 7.38 (2H, br s), 6.88-6.87 (1H, m), 5.91 (2H, s); Anal. Calcd forC₁₅H₁₁N₇O₂•0.3H₂O: C, 55.15; H, 3.58, N, 30.01. Found: C, 55.33; H,3.35; N, 29.64. 206 B 30 IR ν_(max) (film)/cm⁻¹ 3327, 3209, 2987, 1730,1664, 1390, 1168, 959, 745 and 664; NMR δ_(H) (400 MHz, DMSO) 8.16 (1H,s), 8.09 (1H, d, J 8.0 Hz), 7.97-7.92 (2H, m), 7.47 (1H, d, J 7.5 Hz),7.44-7.35 (2H, br s), 7.31 (1H, t, J 7.5 Hz), 7.20 (1H, t, J 7.0 Hz),6.89 (1H, dd, J 3.5, 1.5 Hz), 6.03-5.96 (3H, m) and 1.64 (9H, s) 207 AF71 mp 289.1-289.3° C.; IR ν_(max) (DR)/cm⁻¹ 3442, 3317, 3189, 1649,1607, 1519, 1332, 1118, 1023 and 763; NMR δ_(H) (400 MHz, DMSO) 11.21(1H, br s), 8.13 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.46 (1H, d, 8.0 Hz),7.38 (2H, br s), 7.33 (1H, d, J 8.0 Hz), 7.06 (1H, t, J 8.0 Hz), 6.96(1H, t, J 7.0 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.31 (1H, s) and 5.79(2H, s) 208 B 4 NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m), 7.91-7.88(1H, dd, J 1.5, 3.5 Hz), 7.46-7.36 (2H, s), 6.98-6.96 (1H, d, J 3.5 Hz),6.87-6.84 (1H, dd, J 1.5, 3.5 Hz), 6.72-6.69 (1H, d, J 3.5 Hz),5.76-5.74 (2H, s), 2.52-2.48 (2H, h, J 2.0, 3.5 Hz) and 1.20-1.14 (3H,t, J 7.5 Hz); M/Z 327 (M + H)⁺. 209 B 17 mp > 250° C. dec; IR ν_(max)(DR)/cm⁻¹ 3489, 3316, 2919, 1610, 1326, 1037, 862, 760 and 593; NMRδ_(H) (400 MHz, DMSO) 8.13-8.11 (1H, m), 7.90 (1H, d, J 2.5 Hz), 7.38(2H, br s), 6.92 (1H, d, J 2.0 Hz), 6.88 (1H, d, J 8.0 Hz), 6.86 (1H,dd, J 3.5, 2.0 Hz), 6.79 (1H, dd, J 8.0, 1.5 Hz), 6.00 (2H, s) and 5.56(2H, s). 210 C 36 IR ν_(max) (DR)/cm⁻¹ 3427, 3318, 3201, 2966, 1605,1503, 1415, 1281, 1027 and 762; NMR δ_(H) (400 MHz, DMSO) 1.08 (3H, t, J7.0 Hz), 2.39 (2H, q, J 7.0 Hz), 4.91 (2H, s), 5.44 (2H, s), 6.54 (1H,d, J 8.0 Hz), 6.80-9.62 (2H, m), 6.97 (1H, s), 7.34 (2H, s), 7.89 (1H,s), 8.12 (1H, s). Anal. Calcd for C₁₇H₁₇N₇O•0.6H₂O: C, 58.98; H, 5.30;N, 28.32. Found: C, 59.37; H, 5.02; N, 28.05. 211 AT 13 mp 257.1-257.3°C.; IR ν_(max) (DR)/cm⁻¹ 3491, 3343, 3205, 3131, 2971, 1973, 1691, 1626,1499, 1437, 1239, 1030 and 764; NMR δ_(H) (400 MHz, DMSO) 6.26 (2H, s),6.86-6.91 (1H, m), 7.33 (2H, s), 7.63 (2H, t, J 7.5 Hz), 7.77 (1H, t, J7.5 Hz), 7.94 (1H, d, J 3.0 Hz), 8.11-8.16 (3H, m). 212 R 58 IR ν_(max)(DR)/cm⁻¹ 3321, 1608, 1438, 1304, 1025 and 757; NMR δ_(H) (400 MHz,DMSO) 5.67 (2H, s), 6.86-6.88 (1H, m), 7.05 (1H, d, J 7.5 Hz), 7.20 (1H,dd, J 5.0, 3.5 Hz), 7.35 (1H, t, J 8.0 Hz), 7.39 (2H, s), 7.55-7.58 (1H,m), 7.72 (1H, d, J 7.5 Hz), 7.85 (1H, dd, J 5.0, 1.0 Hz), 7.92 (1H, d, J3.5 Hz), 7.98 (1H, dd, J 3.5, 1.0 Hz), 8.12-8.15 (1H, m), 10.24 (1H, s).213 AU 29 IR ν_(max) (DR)/cm⁻¹ 3285, 1975, 1625, 1461; NMR δ_(H) (400MHz, DMSO) 8.14 (1H, m), 7.92 (1H, d, J 3.0 Hz), 7.80 (1H, t, J 7.5 Hz),7.44 (1H, d, J 7.5 Hz), 6.98 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5Hz), 5.75 (2H, s), 4.52 (2H, s). 214 R 43 IR ν_(max) (DR)/cm⁻¹ 3321,2956, 1610, 1234, 1027and 757; NMR δ_(H) (400 MHz, DMSO) 0.99 (9H, s),2.14 (2H, s), 5.63 (2H, s), 6.85-6.89 (1H, m), 6.94 (1H, d, J 8.0 Hz),7.27 (1H, t, J 7.5 Hz), 7.33-7.45 (3H, m), 7.59 (1H, d, J 9.0 Hz), 7.92(1H, d, J 3.5 Hz), 8.12-8.15 (1H, m). 215 R 52 IR ν_(max) (DR)/cm⁻¹3510, 3278, 1631, 1425, 1293, 1217, 1024 and 757; NMR δ_(H) (400 MHz,DMSO) 0.71-0.79 (4H, m), 1.72 (1H, tt, J 5.5, 7.0 Hz), 5.63 (2H, s),6.85-6.89 (1H, m), 6.96 (1H, d, J 8.0 Hz), 7.27 (1H, t, J 7.5 Hz),7.32-7.45 (3H, m), 7.55 (1H, d, J 8.0 Hz), 7.92 (1H, dd, J 3.5, 1.0 Hz),8.12-8.15 (1H, m), 10.19 (1H, s). Anal. Calcd for C₁₉H₁₇N₇O₂•0.15H₂O: C,60.36; H, 4.61; N, 25.93. Found: C, 60.89; H, 4.62; N, 25.54. 216 B 15mp 178.3-178.5° C.; IR ν_(max) (DR)/cm⁻¹ 3472, 3324, 3194, 2964, 1641,1598, 1510; NMR δ_(H) (400 MHz, DMSO) 8.14 (1H, m), 7.92 (1H, dd, J 1.0,3.5 Hz), 7.66 (1H, t, J 8.0 Hz), 7.35 (2H, br s), 7.17 (1H, d, J 8.0Hz), 6.90 (1H, d, J 8.0 Hz), 6.87 (1H, dd, J 2.0, 3.5 Hz), 5.73 (2H, s),2.63 (2H, t, J 7.5 Hz), 1.59 (2H, sext, J 7.5 Hz), 0.83 (3H, t, J 7.5Hz); Anal. Calcd for C₁₇H₁₇N₇O•0.1C₄H₈O₂: C, 60.72; H, 5.21, N, 28.49.Found: C, 60.85; H, 5.22; N, 28.29. 217 B 16 mp 146.7-149.3° C.; IRν_(max) (DR)/cm⁻¹ 3518, 3323, 2955, 1605, 1511; NMR δ_(H) (400 MHz,DMSO) 8.14-8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.79 (1H, t, J 7.5 Hz),7.35 (2H, br s), 7.35 (1H, d, J 7.5 Hz), 7.05 (1H, d, J 7.5 Hz), 6.87(1H, dd, J 1.5, 3.5 Hz), 5.75 (2H, s), 4.46 (2H, s), 3.22 (2H, d, J 6.5Hz), 1.77-1.87 (1H, m), 0.85 (6H, d, J 6.5 Hz); Anal. Calcd forC₁₉H₂₁N₇O₂•0.5H₂O: C, 58.75; H, 5.71, N, 25.24. Found: C, 58.87; H,5.49; N, 24.92. 218 B 14 mp 196.0-196.1° C.; IR ν_(max) (DR)/cm⁻¹ 3481,3325, 3203, 1646, 1607, 1518, 1488; NMR δ_(H) (400 MHz, DMSO) 8.14 (1H,m), 7.92 (1H, d, J 3.5 Hz), 7.80 (1H, t, J 7.5 Hz), 7.50 (1H, d, J 7.5Hz), 7.38 (2H, br s), 7.04 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5Hz), 5.77 (2H, s), 4.64 (2H, s). 219 C 37 IR ν_(max) (DR)/cm⁻¹ 3480,3379, 3199, 2958, 2761, 2104, 1879, 1776, 1659, 1516, 1439, 1334, 1024,762 and 575; NMR δ_(H) (400 MHz, DMSO) 1.10 (6H, d, J 7.0 Hz), 2.92 (1H,sept, J 6.5 Hz), 4.93 (2H, s), 5.44 (2H, s), 6.54 (1H, d, J 8.0 Hz),6.80-6.88 (2H, m), 7.09 (1H, d, J 2.0 Hz), 7.34 (2H, s), 7.88 (1H, d, J3.5 Hz), 8.10-8.13 (1H, m). Anal. Calcd for C₁₈H₁₉N₇O•0.3H₂O: C, 60.93;H, 5.57; N, 27.63. Found: C, 60.77; H, 5.50; N, 27.42. 220 AV 26 mp223.3-223.4° C.; NMR δ_(H) (400 MHz, DMSO) 8.14 (1H, m), 7.92 (1H, dd, J1.0, 3.5 Hz), 7.82 (1H, t, J 7.5 Hz), 7.37 (1H, d, J 7.5 Hz), 7.36 (2H,br s), 7.07 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5 Hz), 5.78 (2H,s), 4.18 (2H, s). 221 AW 7 NMR δ_(H) (400 MHz, DMSO) 9.48-9.45 (1H, s),8.12-8.10 (1H, m), 7.90-7.88 (1H, dd, J 1.0, 3.5 Hz), 7.36-7.30 (2H, s),7.17-7.12 (2H, dd, J 2.0, 8.5 Hz), 6.86-6.84 (1H, dd, J 2.0, 3.5 Hz),6.74-6.70 (2H, dd, J 2.0, 8.5 Hz) and 5.53-5.51 (2H, s); M/Z 309 (M +H)⁺. 222 B 18 IR ν_(max) (DR)/cm⁻¹ 3483, 3319, 3200, 2961, 1953, 1709,1612, 1439, 1343, 1220, 995 and 761; NMR δ_(H) (400 MHz, DMSO) 6.37 (2H,s), 6.86-6.91 (1H, m), 7.35 (2H, s), 7.94 (1H, d, J 3.0 Hz), 8.15 (1H,s), 8.37 (2H, d, J 8.5 Hz), 8.43 (2H, d, J 8.5 Hz). Anal. Calcd forC₁₆H₁₁N₇O₄•0.2H₂O: C, 52.09; H, 3.11; N, 26.58. Found: C, 51.94; H,3.05; N, 26.27. 223 B 41 IR ν_(max) (DR)/cm⁻¹ 4013, 3601, 3456, 3209,2959, 2237, 1938, 1708, 1625, 1505, 1171, 1002, 827 and 733; NMR δ_(H)(400 MHz, DMSO) 6.33 (2H, s), 6.84-6.91 (1H, m), 7.34 (2H, s), 7.94 (1H,d, J 3.5 Hz), 8.09-8.18 (3H, m), 8.28 (2H, d, J 8.0 Hz). Anal. Calcd forC₁₇H₁₁N₇O₂•0.7H₂O: C, 57.05; H, 3.49; N, 27.39. Found: C, 56.97; H,3.12; N, 27.37. 224 AX 54 IR ν_(max) (DR)/cm⁻¹ 3423, 3321, 3212, 1641,1511, 1420, 1316, 1136 and 780; NMR δ_(H) (400 MHz, DMSO) 0.87 (3H, t, J7.5 Hz), 1.54-1.66 (2H, m), 2.96-3.04 (2H, m), 5.65 (2H, s), 6.85-6.88(1H, m), 7.00-7.03 (2H, m), 7.10-7.16 (1H, m), 7.30 (1H, t, J 7.5 Hz),7.36 (2H, s), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.12-8.15 (1H, m), 9.79 (1H,s). Anal. Calcd for C₁₈H₁₉N₇O₃S: C, 52.29; H, 4.63; N, 23.70. Found: C,52.22; H, 4.70; N, 23.36. 225 AX 47 IR ν_(max) (DR)/cm⁻¹ 3477, 3319,3114, 1609, 1479, 1414, 1349, 1162, 956 and 763; NMR δ_(H) (400 MHz,DMSO) 5.63 (2H, s), 5.85-6.89 (1H, m), 6.92 (1H, t, J 1.5 Hz), 7.02-7.11(3H, m), 7.26-7.33 (2H, m), 7.37 (2H, s), 7.93 (1H, dd, J 3.5, 1.0 Hz),8.12-8.15 (1H, m), 10.62 (1H, s). 226 AY 58 mp 221.4-221.5° C.; IRν_(max) (DR)/cm⁻¹ 3569, 3134, 2701, 2421, 1656, 1460; NMR δ_(H) (400MHz, DMSO) 8.14 (1H, m), 7.92 (1H, dd, J 1.0, 3.5 Hz), 7.88 (1H, t, J7.5 Hz), 7.48 (1H, d, J 7.5 Hz), 7.16 (1H, d, J 7.5 Hz), 6.88-6.87 (1H,m), 5.80 (2H, s), 4.27-4.24 (2H, m), 2.60-2.56 (3H, m). 227 B 24 IRν_(max) (DR)/cm⁻¹ 4011, 3491, 3377, 3210, 3125, 2975, 2663, 2106, 1924,1740, 1618, 1438, 1201, 1004, 796 and 752; NMR δ_(H) (400 MHz, DMSO)1.14 (6H, t, J 6.5 Hz), 3.46 (4H, q, J 6.5 Hz), 6.00 (2H, s), 6.76 (2H,d, J 9.0 Hz), 6.87 (1H, s), 7.26 (2H, s), 7.85-7.97 (3H, m), 8.13 (1H,s), Anal. Calcd for C₂₀H₂₁N₇O₂•0.6 H₂O: C, 59.72; H, 5.56; N, 24.38.Found: C, 60.00; H, 5.40; N, 24.03. 228 B 26 mp 164.3-169.3° C.; IRν_(max) (DR)/cm⁻¹ 3376, 3199, 2964, 1659, 1613, 1516, 1441; NMR δ_(H)(400 MHz, DMSO) 8.53 (1H, d, J 2.0 Hz), 8.12-8.11 (1H, m), 7.89 (1H, d,J 3.5 Hz), 7.62 (1H, dd, J 2.5, 8.0 Hz), 7.35 (2H, br s), 7.26 (1H, d, J7.5 Hz), 6.85 (1H, dd, J 1.5, 3.5 Hz), 5.67 (2H, s), 2.99 (1H, sept, J7.0 Hz), 1.20 (6H, d, J 7.0 Hz); Anal. Calcd for C₁₇H₁₇N₇O•0.5H₂O: C,59.29; H, 5.27, N, 28.47. Found: C, 59.28; H, 5.16; N, 28.23. 229 B 40mp 258.2-258.4° C.; IR ν_(max) (DR)/cm⁻¹ 3367, 3200, 2932, 1671, 1243,1178, 1033, 797 and 610; NMR δ_(H) (400 MHz, DMSO) 8.12-8.07 (3H, m),7.91 (1H, d, J 3.5 Hz), 7.15-7.09 (4H, m), 6.85 (1H, dd, J 3.5, 1.5 Hz),6.10 (2H, s) and 3.89 (3H, s). 230 B 25 IR ν_(max) (DR)/cm⁻¹ 3436, 3320,3208, 2977, 1609, 1370, 1323, 1155, 1025, 840 and 768; NMR δ_(H) (400MHz, DMSO) 8.12-8.10 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.78 (1H, d, J 4.0Hz), 7.73 (1H, d, J 2.5 Hz), 7.33 (2H, br s), 6.88-6.84 (2H, m), 6.76(1H, d, J 4.0 Hz), 6.07 (2H, s) and 1.50 (9H, s). 231 AF 76 mp321.8-322.2° C.; IR ν_(max) (DR)/cm⁻¹ 3993, 3233, 1645, 1515, 1437,1336, 1102, 854 and 759; NMR δ_(H) (400 MHz, DMSO) 11.56 (1H, br s),8.13-8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.58 (1H, d, J 2.0 Hz), 7.55(1H, t, J 3.5 Hz), 7.42 (2H, br s), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.73(1H, d, J 2.0 Hz), 6.52 (1H, dd, J 3.0, 2.0 Hz) and 5.94 (2H, s). 232 AX20 IR ν_(max) (DR)/cm⁻¹ 3216, 1713, 1610, 1505, 1421, 1185, 1124, 1026,886 and 763; NMR δ_(H) (400 MHz, DMSO) 2.13 (3H, s), 2.35 (3H, s), 5.62(2H, s), 6.85-6.88 (1H, m), 6.90-6.94 (1H, m), 6.98-7.03 (1H, m), 7.11(1H, d, J 8.0 Hz), 7.30 (1H, t, J 7.5 Hz), 7.31 (2H, s), 7.91 (1H, d, J3.5 Hz), 8.11-8.14 (1H, m), 10.46 (1H, s). 233 AV 40 mp 219.7-222.3° C.;IR ν_(max) (DR)/cm⁻¹ 3326, 3191, 2821, 2772, 1595, 1504, 1432; NMR δ_(H)(400 MHz, DMSO) 8.13-8.12 (1H, m), 7.91 (1H, dd, J 1.0, 3.5 Hz), 7.74(1H, t, J 7.5 Hz), 7.35 (1H, d, J 7.5 Hz), 7.31 (2H, br s), 6.98 (1H, d,J 7.5 Hz), 6.86 (1H, dd, J 2.0, 3.5 Hz), 5.74 (2H, s), 3.46 (2H, s),2.15 (6H, s); Anal. Calcd for C₁₇H₁₈N₈O: C, 58.28; H, 5.18, N, 31.97.Found: C, 57.94; H, 5.17; N, 31.70. 234 AV 55 mp 168.3-168.5° C.; IRν_(max) (DR)/cm⁻¹ 3416, 3322, 3180, 2911, 1646, 1612, 1509, 1436; NMRδ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m), 7.91 (1H, dd, J 1.0, 3.5 Hz),7.74 (1H, t, J 7.5 Hz), 7.32 (1H, d, J 7.5 Hz), 7.31 (2H, br s), 7.02(1H, d, J 7.5 Hz), 6.87-6.86 (1H, m), 5.75 (2H, s), 3.69 (2H, s), 1.92(3H, s); Anal. Calcd for C₁₆H₁₅N₇OS•0.2H₂O: C, 53.83; H, 4.35, N, 27.46.Found: C, 53.74; H, 4.29; N, 27.13. 235 B 3 mp 231.6-231.7° C.; IRν_(max) (DR)/cm⁻¹ 3642, 3320, 3198, 1727, 1533, 1437, 1223, 1029, 842and 639; NMR δ_(H) (400 MHz, DMSO) 8.18 (1H, d, J 7.5 Hz), 8.13 (1H, s),8.00-7.93 (2H, m), 7.91 (1H, d, J 3.5 Hz), 7.89-7.82 (1H, m), 7.34 (2H,br s), 6.87 (1H, dd, J 3.5, 1.5 Hz) and 6.01 (2H, s). 236 AX 32 NMRδ_(H) (400 MHz, DMSO) 2.19 (3H, s), 3.50 (3H, s), 5.58 (2H, s),6.84-6.97 (3H, m), 7.08 (1H, d, J 8.0 Hz), 7.20 (1H, t, J 7.5 Hz), 7.35(2H, s), 7.58 (1H, s), 7.91 (1H, d, J 3.0 Hz), 8.13 (1H, s) and 10.14(1H, s); retention time 0.97 min. 237 AV 40 mp 259.3-259.4° C.; IRν_(max) (DR)/cm⁻¹ 3323, 3202, 1607, 1511; NMR δ_(H) (400 MHz, DMSO)8.12-8.11 (2H, m), 7.91 (2H, dd, J 1.0, 3.5 Hz), 7.70-7.66 (2H, m), 7.30(4H, br s), 7.10 (4H, d, J 8.0 Hz), 6.85 (2H, dd, J 1.5, 3.5 Hz), 5.73(4H, s), 4.23 (4H, s), 2.78 (3H, s). 238 AV 17 mp 238.2-238.6° C.; IRν_(max) (DR)/cm⁻¹ 3189, 2908, 1653, 1592, 1470; NMR δ_(H) (400 MHz,DMSO) 8.13-8.12 (1H, m), 7.91 (1H, d, J 3.0 Hz), 7.85 (1H, t, J 7.5 Hz),7.43 (1H, d, J 7.5 Hz), 7.30 (2H, br s), 7.23 (1H, d, J 7.5 Hz),6.87-6.85 (1H, m), 5.81 (2H, s), 4.56 (2H, s), 2.87 (3H, s). 239 AV 71mp 205.8-206.0° C.; IR ν_(max) (Nujol)/cm⁻¹ 3502, 3304, 3185, 2923,1628, 1510; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m), 7.92 (1H, d, J3.0 Hz), 7.83 (1H, t, J 8.0 Hz), 7.33 (1H, d, J 8.0 Hz), 7.30 (2H, brs), 7.17 (1H, d, J 8.0 Hz), 6.87-6.86 (1H, m), 5.79 (2H, s), 4.31 (2H,s), 2.84 (3H, s), 2.67 (3H, s); Anal. Calcd for C₁₇H₁₈N₈O₃S: C, 49.27;H, 4.38, N, 27.02. Found: C, 49.14; H, 4.49; N, 26.74. 240 C 24 mp254.3-254.5.° C.; IR ν_(max) (DR)/cm⁻¹ 3443, 3342, 3187, 1647, 1593,1513, 1414, 1300, 1268 and 1225; NMR δ_(H) (400 MHz, DMSO) 7.37 (2H, s),6.96 (1H, t, J 7.8 Hz), 6.46 (1H, dd, J 1.0, J 8.0 Hz), 6.40 (2H, d, J7.5 Hz), 6.33 (1H, s), 5.56 (2H, s), 5.2 (2H, s), 2.5 (3H, s) and 2.44(3H, s). 241 C 17 NMR δ_(H) (400 MHz, DMSO) 8.11-8.09 (1H, m), 7.89-7.86(1H, dd, J 1.0, 3.5 Hz), 7.32-7.27 (2H, s), 7.22-6.95 (1H, t, J 9.0 Hz),6.85-6.83 (1H, dd, J 2.0, 3.5 Hz), 6.35-6.29 (2H, m), 5.48-5.46 (2H, s)and 5.46-5.44 (2H, s); Retention time 1.18 min. 242 B 15 IR ν_(max)(DR)/cm⁻¹ 3850, 3667, 2923, 1730, 1601, 1464, 1023, 751 and 593; NMRδ_(H) (400 MHz, DMSO) 3.68 (1H, dd, J 16.0, 5.5 Hz), 3.88 (1H, dd, J16.0, 9.0 Hz), 6.05 (1H, dd, J 8.5, 5.5 Hz), 6.84-6.89 (1H, m), 7.29(2H, s), 7.57 (1H, t, J 7.0 Hz), 7.72 (1H, d, J 7.5 Hz), 7.78-7.87 (2H,m), 7.91 (1H, d, J 3.5 Hz), 8.13 (1H, s). Anal. Calcd forC₁₇H₁₂N₆O₂•0.2H₂O: C, 60.87; H, 3.72; N, 25.02. Found: C, 60.89; H,3.68; N, 24.85. 243 AF 53 mp > 300° C. dec; IR ν_(max) (DR)/cm⁻¹ 3212,2923, 1642, 1605, 1510, 1461, 1377, 1023 and 757; NMR δ_(H) (400 MHz,DMSO) 11.16 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.44-7.36(3H, m), 7.29 (1H, s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.58 (1H, s),6.42-6.38 (1H, m), 5.87 (2H, s) and 2.27 (3H, s). 244 BB 7 IR ν_(max)(Nujol)/cm⁻¹ 3319, 2924, 1646, 1606, 1462; NMR δ_(H) (400 MHz, DMSO)9.54 (1H, s), 8.27-8.26 (1H, m), 8.12-8.11 (1H, m), 7.90 (1H, d, J 3.5Hz), 7.71 (1H, d, J 8.0 Hz), 7.32 (2H, br s), 7.17-7.15 (1H, m),7.11-7.09 (1H, m), 6.86-6.85 (1H, m), 5.59 (2H, s), 2.18 (3H, s). 245 B22 IR ν_(max) (Nujol)/cm⁻¹ 3849, 3500, 3298, 3174, 2924, 1698, 1631,1604, 1456, 1379, 1226, 1027, 953 and 753; NMR δ_(H) (400 MHz, DMSO)1.91 (3H, d, J 7.0 Hz), 6.63 (1H, q, J 7.0 Hz), 6.84-6.87 (1H, m), 7.32(2H, s), 7.54 (2H, t, J 8.0 Hz), 7.66 (1H, tt, J 7.5, 2.0 Hz), 7.88 (1H,d, J 3.5 Hz), 7.98-8.03 (2H, m), 8.11-8.12 (1H, m). Anal. Calcd forC₁₇H₁₄N₆O₂: C, 61.07; H, 4.22; N, 25.12. Found: C, 60.72; H, 4.27; N,24.75. 246 BE 81 IR ν_(max) (Nujol;)/cm⁻¹ 3313, 3189, 2924, 1605, 1461,1377, 1236, 1026 and 762; NMR δ_(H) (400 MHz, DMSO) 11.62 (1H, br s),8.11 (1H, dd, J 2.0, 1.0 Hz), 7.90 (1H, d, J 3.5 Hz), 7.41 (1H, t, J 2.5Hz), 7.37-7.29 (3H, m), 6.94 (1H, d, J 11.0 Hz), 6.85 (1H, dd, J 3.5,2.0 Hz) 6.52-6.47 (1H, m) and 5.71 (2H, s). 247 B 28 mp 134.5-134.6° C.;IR ν_(max) (Nujol)/cm⁻¹ 3306, 3189, 2924, 1635, 1610, 1580; NMR δ_(H)(400 MHz, DMSO) 8.13-8.12 (1H, m), 7.92-7.91 (1H, m), 7.79-7.75 (1H, m),7.35 (1H, d, J 8.0 Hz), 7.31 (2H, br s), 7.03 (1H, d, J 7.5 Hz), 6.86(1H, dd, J 3.5, 1.5 Hz), 5.74 (2H, s), 4.46 (2H, s), 3.65 (1H, sept, J6.0 Hz), 1.12 (6H, d, J 6.0 Hz); Anal. Calcd for C₁₈H₁₉N₇O₂•1.2H₂O: C,55.86; H, 5.57, N, 25.33. Found: C, 55.80; H, 5.41; N, 25.05. 248 B 11mp 158.9.-161.3° C.; IR ν_(max) (Nujol)/cm⁻¹ 3301, 3185, 2923, 1636,1611, 1570, 1536, 1501, 1324 and 1210; NMR δ_(H) (400 MHz, DMSO) 7.88(1H, d, J 3.0 Hz), 7.66 (1H, t, J 7.5 Hz), 7.27 (2H, br s) 7.18 (1H, d,J 7.5 Hz), 6.89 (1H, d, J 7.5 Hz), 6.51 (1H, dd, J 1.0, J 3.5 Hz), 5.71(2H, s), 2.69 (2H, q, J 7.5 Hz), 2.46 (3H, s) and 1.15 (3H, J 7.5 Hz).249 BE 76 IR ν_(max) (DR;)/cm⁻¹ 3319, 2928, 1605, 1334, 1226, 1027, 737and 528; NMR δ_(H) (400 MHz, DMSO) 11.47 (1H, s), 8.14-8.09 (1H, m) 7.89(1H, d, J 3.5 Hz), 7.48 (1H, d, J 3.0 Hz), 7.38-7.27 (3H, m), 6.94 (1H,d, J 13.0 Hz), 6.85 (1H, dd, J 3.5, 2.0 Hz), 6.52-6.47 (1H, m) and 5.81(2H, s). 250 BE 68 IR ν_(max) (DR)/cm⁻¹ 3318, 2923, 1640, 1579, 1455,1377, 1079, 1022, 750 and 588; NMR δ_(H) (400 MHz, DMSO) 11.13 (1H, brs), 8.23 (1H, s), 8.05-8.04 (1H, m), 7.43 (1H, d, J 3.5 Hz), 7.30 (2H,s), 7.00 (1H, t, J 7.0 Hz), 6.90 (2H, s), 6.80-6.77 (1H, m), 6.73 (1H,d, J 6.5 Hz), 6.51 (1H, s)and 5.63 (2H, s). 251 BE 42 mp 294.0-294.2°C.; IR ν_(max) (DR)/cm⁻¹ 3498, 3414, 1612, 1318, 1235, 102, 765 and 589;NMR δ_(H) (400 MHz, DMSO) 11.24 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J3.5 Hz), 7.53 (1H, s), 7.39 (1H, t, J 2.5 Hz) 7.36-7.26 (3H, m),6.88-6.82 (1H, m), 6.43-6.38 (1H, m) and 5.76 (2H, s) 252 BF 44 mp200.2.-201.2° C. IR ν_(max) (DR)/cm⁻¹ 3390, 3205, 2924, 1725, 1648,1603, 1508, 1423, 1332, 1277 and 1158; NMR δ_(H) (400 MHz, DMSO) 8.12(1H, s), 7.90 (1H, d, J 3.5 Hz), 7.35-7.25 (4H, m), 7.07-6.97 (3H, m),6.86 (1H, dd, J 1.5, J 3.5 Hz), 6.45 (2H, t, J 7.5 Hz), 6.37 (1H, s),6.32 (1H, t, J 6.0 Hz), 5.49 (2H, s) and 4.16 (2H, s, J 6.0 Hz). 253 B18 mp 181.8-182.1° C.; IR ν_(max) (DR)/cm⁻¹ 3362, 3208, 2988, 1654,1601, 1513; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m), 7.91 (1H, d, J3.5 Hz), 7.68 (1H, m), 7.29 (2H, br s), 6.87-6.85 (1H, m), 6.74 (1H, d,J 7.5 Hz), 6.68 (1H, d, J 8.0 Hz), 5.69 (2H, s), 4.07 (2H, q, J 7.0 Hz),1.12 (3H, t, J 7.0 Hz). 254 B 14 mp 190.8-190.9° C.; IR ν_(max)(DR)/cm⁻¹ 3514, 3292, 3158, 2984, 1615, 1500; NMR δ_(H) (400 MHz, DMSO)7.88 (1H, d, J 3.5 Hz), 7.65 (1H, dd, J 7.0, 8.0 Hz), 7.25 (2H, br s),6.72 (1H, d, J 7.0 Hz), 6.68 (1H, d, J 8.0 Hz), 6.52-6.50 (1H, m), 5.67(2H, s), 4.08 (2H, q, J 7.0 Hz), 2.46 (3H, s), 1.12 (3H, t, J 7.0 Hz).255 BF 20 mp 184.5-184.6° C.; IR ν_(max) (DR)/cm⁻¹ 3202, 1649, 1601,1509, 1436, 1331, 1277 and 1221; NMR δ_(H) (400 MHz, DMSO) 8.43 (1H, d,J 4.89 Hz), 8.12 (1H, dd, J 0.8, 3.5 Hz), 7.91 (1H, dd, J 0.9, 3.5 Hz),7.65 (1H, td, J 1.7, 7.7 Hz), 7.30 (2H, br s), 7.25 (1H, d, J 7.9 Hz),7.15 (1H, dd, J 4.9, 7.5 Hz), 7.0 (1H, t, J 7.8 Hz), 6.86 (1H, dd, J1.7, 3.5 Hz), 6.48-6.36 (4H, m), 5.49 (2H, s), 4.27 (2H, s); Anal. Calcdfor C₂₁H₁₈N₈O•0.3H₂O: C, 62.46; H, 4.64, N, 27.75. Found: C, 62.66; H,4.57; N, 27.36. 256 B 6 Mp 167.6-168.1° C. IR ν_(max) (DR)/cm⁻¹ 3509,3304, 3178, 1609, 1494, 1421, 1325, 1127, 839 and 752. NMR δ_(H) (400MHz, DMSO) 2.05 (3H, d, J 7.0 Hz), 6.14 (1H, q, J 7.0 Hz), 6.84-6.88(1H, m), 7.30 (2H, s), 7.52 (2H, d, J 8.5 Hz), 7.73 (2H, d, J 8.0 Hz),7.91 (1H, dd, J 3.5, 1.0 Hz), 8.11-8.13 (1H, m). Anal. Calcd forC₁₇H₁₃N₆F₃O: C, 54.55; H, 3.50; N, 22.44. Found: C, 54.52; H, 3.65; N,22.06. 257 BE 75 IR ν_(max) (DR)/cm⁻¹ 3459, 3348, 3187, 2960, 1648,1513, 1351, 1244, 1011, 837 and 759; NMR δ_(H) (400 MHz, DMSO) 11.18(1H, br s), 8.11 (1H, s), 7.89 (1H, d, J 3.0 Hz), 7.42 (1H, d, J 7.5Hz), 7.37-7.26 (3H, m), 7.21 (1H, d, J 11.0 Hz), 6.89-6.81 (1H, m),6.43-6.37 (1H, s) and 5.72 (2H, s). 258 BE 94 mp > 300° C. dec; IRν_(max) (DR)/cm⁻¹ 3441, 3318, 2990, 1612, 1285, 1083, 839 and 593; NMRδ_(H) (400 MHz, DMSO) 11.29 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J 3.5Hz), 7.41-7.29 (3H, m), 7.22 (1H, dd, J 10.0, 2.5 Hz), 6.90 (1H, dd, J9.5, 2.5 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.30 (1H, s) and 5.79 (2H,s). 259 B 50 mp 228.4-228.5° C.; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12(1H, m), 7.91 (1H, d, J 3.5 Hz), 7.34 (2H, br s), 7.18 (2H, s),6.87-6.85 (1H, m), 5.67 (2H, s), 2.22 (6H, s). 260 B 8 mp 150.3-151.0°C. IR ν_(max) (DR)/cm⁻¹ 3510, 3306, 3183, 1633, 1495, 1423, 1240, 1029and 753; NMR δ_(H) (400 MHz, DMSO) 2.02 (3H, d, J 7.0 Hz), 6.05 (1H, q,J 7.0 Hz), 6.83-6.88 (1H, m), 7.10-7.22 (3H, m), 7.30 (2H, s), 7.40 (1H,dt, J 8.0, 6.5 Hz), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.10-8.13 (1H, m).Anal. Calcd for C₁₆H₁₃N₆OF•0.25H₂O: C, 58.44; H, 4.14; N, 25.56. Found:C, 58.48; H, 3.98; N, 25.40. 261 BE 91 IR ν_(max) (DR)/cm⁻¹ 3472, 3318,3184, 2922, 1651, 1595, 1478, 1417, 1329, 1218, 1097, 1015, 870, 767and545; NMR δ_(H) (400 MHz, DMSO) 11.50 (1H, s), 8.11 (1H, s), 7.90 (1H, d,J 3.5 Hz), 7.47 (1H, s), 7.42 (1H, t, J 3.0 Hz), 7.33 (2H, s), 7.19 (1H,s), 6.86-6.84 (1H, m), 6.53-6.51 (1H, m), 5.71 (2H, s). 262 C 34 mp250.1-261.3° C.; IR ν_(max) (DR)/cm⁻¹ 3325, 3205, 2968, 1603, 1488; NMRδ_(H) (400 MHz, DMSO) 8.11-8.10 (1H, m), 7.89-7.87 (1H, m), 7.28 (2H, brs), 6.85-6.83 (1H, m), 6.81 (2H, s), 5.40 (2H, s), 4.56 (2H, br s), 2.03(6H, s). 263 K 72 IR ν_(max) (DR)/cm⁻¹ 2825, 2021, 1645, 1453, 1394,1286, 1171, 1030, 779 and 619; NMR δ_(H) (400 MHz, DMSO) 2.02 (3H, d, J7.0 Hz), 6.07 (1H, q, J 7.0 Hz), 6.85-6.88 (1H, m), 7.13-7.18 (1H, m),7.25 (1H, d, J 8.5 Hz), 7.36 (1H, d, J 8.0 Hz), 7.47 (1H, t, J 7.5 Hz),7.92 (1H, d, J 3.5 Hz), 8.12-8.14 (1H, m). Anal. Calcd forC₁₆H₁₅N₇O•2HCl•0.8H₂O: C, 47.02; H, 4.59; N, 23.99. Found: C, 46.87; H,4.43; N, 23.71. 264 B 26 mp 162.0-162.6° C.; IR ν_(max) (DR)/cm⁻¹ 3319,3206, 2932, 1644, 1505; NMR δ_(H) (400 MHz, DMSO) 8.13-8.12 (1H, m),7.92-7.91 (1H, m), 7.68-7.64 (1H, m), 7.31 (2H, br s), 7.21 (1H, d, J7.5 Hz), 6.92 (1H, d, J 8.0 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.74 (2H,s), 3.58 (2H, t, J 6.5 Hz), 3.16 (3H, s), 2.84 (2H, t, J 6.5 Hz); M/Z352 (M + H)⁺. 265 B 15 NMR δ_(H) (400 MHz, DMSO) 8.12-8.11 (1H, m),7.92-7.90 (1H, m), 7.47 (1H, d, J 8.0 Hz), 7.28 (2H, br s), 6.91 (1H, d,J 8.0 Hz), 6.86 (1H, dd, J 2.0, 3.5 Hz), 5.73-5.69 (1H, m), 2.60-2.46(2H, m), 2.39 (3H, s), 2.20 (3H, s), 0.87 (3H, t, J 7.0 Hz); M/Z 350(M + H)⁺. 266 AK 99 NMR δ_(H) (400 MHz, DMSO) 8.22-8.17 (2H, m), 7.94(1H, d, J 2.01 Hz), 7.73-7.63 (2H, m), 7.37 (1H, d, J 2.5 Hz) and 5.86(2H, s); M/Z 338 (M + H)⁺; Retention time 1.74 min. 267 B 58 mp255.6-255.7° C.; IR ν_(max) (DR)/cm⁻¹ 3512, 3294, 3179, 2960, 2692,1745, 1638, 1432 and 1371; NMR δ_(H) (400 MHz, DMSO) 7.88 (1H, d, J 3.51Hz), 7.81 (1H, dd, J 1.0, J 8.0 Hz), 7.46-7.29 (2H, br s), 7.40 (1H, t,J 7.8 Hz), 7.23 (1H, d, J 8.0 Hz), 6.51 (1H, dd, J 1.0, 3.5 Hz), 5.78(2H, s) and 2.46 (6H, s). 268 B 40 mp 248.1-249.0° C. IR ν_(max)(DR)/cm⁻¹ 3507, 3308, 3190, 2952, 1626, 1571, 1519, 1434, 1348 and 1291;NMR δ_(H) (400 MHz, DMSO) 8.22 (2H, d, J 8.5 Hz), 7.89 (1H, d, J 3.5Hz), 7.49 (2H, d, J 9.0 Hz), 7.36 (2H, br s), 6.52 (1H, dd, J 1.0, 3.5Hz), 5.83 (2H, s) and 2.46 (3H, s). 269 B 18 NMR δ_(H) (400 MHz, DMSO)8.14-8.12 (1H, m), 7.92-7.90 (1H, dd, J 1.0, 3.5 Hz), 7.42-7.34 (2H, s),7.26-7.25 (4H, s), 6.87-6.85 (1H, dd, J 1.5, 3.5 Hz), 5.66-5.64 (2H, s),3.15-3.13 (3H, s) and 1.38-1.36 (9H, s). 270 H 46 NMR δ_(H) (400 MHz,DMSO) 8.22-8.13 (2H, m), 7.75-7.65 (3H, m), 7.59 (1H, dd, J 1.5, J 3.0Hz), 7.34 (2H, br s), 6.96 (1H, dd, J 1.5, J 3.5 Hz), 6.45 (1H, t, J 3.2Hz), 5.85 (2H, s) and 1.22 (9H, s); M/Z 437 (M + H)⁺; Retention time4.36 min. 271 Q 40 NMR δ_(H) (400 MHz, DMSO) 8.21-8.17 (2H, m),7.71-7.63 (2H, m), 7.48 (2H, br s), 5.87 (2H, s), 2.50 (3H, s) and 2.44(3H, s); M/Z 383 (M + H)⁺; Retention time 3.69 min. 272 B NMR δ_(H) (400MHz, DMSO) 8.18 (1H, dd, J 9.6, 2.0 Hz), 8.13 (1H, d, J 1.6 Hz), 8.05(1H, dd, J 8.4, 2.4 Hz), 7.90 (1H, d, J 3.2 Hz), 7.45 (1H, t, J 8.0 Hz),7.38 (2H, br s), 6.86 (1H, dd, J 3.6, 2.0 Hz) and 5.84 (2H, s). 273 BNMR δ_(H) (400 MHz, DMSO) 8.13-8.09 (1H, m), 7.89 (1H, d, J 3.5 Hz),7.66 (1H, d, J 3.5 Hz), 7.39 (1H, s), 7.29 (2H, br s), 6.85 (1H, dd, J3.5, 2.0 Hz), 6.68 (1H, d, J 3.5 Hz), 6.65 (1H, s), 2.27 (3H, s) and1.52 (9H, s). 274 BA 99 IR ν_(max) (Nujol)/cm⁻¹ 3313, 2923, 1693, 1603;NMR δ_(H) (400 MHz, DMSO) 8.78 (1H, br s), 8.12-8.11 (1H, m), 7.90 (1H,d, J 3.5 Hz), 7.34-7.31 (3H, m), 7.13-7.12 (1H, m), 7.08-7.05 (1H, m),6.86-6.85 (1H, m), 5.58 (2H, s), 4.08 (2H, q, J 7.0 Hz), 2.16 (3H, s),1.21 (3H, t, J 7.0 Hz).Adenosine Receptor BindingBinding Affinities at hA_(2A) Receptors

The compounds were examined in an assay measuring in vitro binding tohuman adenosine A_(2A) receptors by determining the displacement of theadenosine A_(2A) receptor selective radioligand [³H]-CGS 21680 usingstandard techniques. The results are summarised in Table 3.

TABLE 3 Example K_(i) (nM) Example 3 3 Example 4 4 Example 5 3 Example 83 Example 11 2 Example 12 7 Example 13 2 Example 15 4 Example 41 2Example 57 2 Example 78 3 Example 92 2 Example 107 2 Example 120 1Example 149 1 Example 156 2 Example 169 2 Example 188 1 Example 202 1Example 209 1 Example 221 2 Example 233 4 Example 255 4Evaluation of Potential Anti-Parkinsonian Activity In VivoHaloperidol-Induced Hypolocomotion Model

It has previously been demonstrated that adenosine antagonists, such astheophylline, can reverse the behavioural depressant effects of dopamineantagonists, such as haloperidol, in rodents (Mandhane S. N. et al.,Adenosine A₂ receptors modulate haloperidol-induced catalepsy in rats.Eur. J. Pharmacol. 1997, 328, 135-141). This approach is also considereda valid method for screening drugs with potential antiparkinsonianeffects. Thus, the ability of novel adenosine antagonists to blockhaloperidol-induced deficits in locomotor activity in mice can be usedto assess both in vivo and potential antiparkinsonian efficacy.

Method

Female TO mice (25-30 g) obtained from TUCK, UK, are used for allexperiments. Animals are housed in groups of 8 [cage size−40 (width)×40(length)×20 (height)cm] under 12 hr light/dark cycle (lights on 08:00hr), in a temperature (20±2° C.) and humidity (55±15%) controlledenvironment. Animals have free access to food and water, and are allowedat least 7 days to acclimatize after delivery before experimental use.

Drugs

Liquid injectable haloperidol (1 ml Serenance ampoules from BakerNorton, Harlow, Essex, each containing haloperidol BP 5 mg, batch #P424) are diluted to a final concentration of 0.02 mg/ml using saline.Test compounds are typically prepared as aqueous suspensions in 8%Tween. All compounds are administered intraperitoneally in a volume of10 ml/kg.

Procedure

1.5 hours before testing, mice are administered 0.2 mg/kg haloperidol, adose that reduces baseline locomotor activity by at least 50%. Testsubstances are typically administered 5-60 minutes prior to testing. Theanimals are then placed individually into clean, clear polycarbonatecages [20 (width)×40 (length)×20 (height) cm, with a flat perforated,Perspex lid]. Horizontal locomotor activity is determined by placing thecages within a frame containing a 3×6 array of photocells linked to acomputer, which tabulates beam breaks. Mice are left undisturbed toexplore for 1 hour, and the number of beams breaks made during thisperiod serves as a record of locomotor activity which is compared withdata for control animals for statistically significant differences.

6-OHDA Model

Parkinson's disease is a progressive neurodegenerative disordercharacterised by symptoms of muscle rigidity, tremor, paucity ofmovement (hypokinesia), and postural instability. It has beenestablished for some time that the primary deficit in PD is a loss ofdopaminergic neurones in the substantia nigra which project to thestriatum, and indeed a substantial proportion of striatal dopamine islost (ca 80-85%) before symptoms are observed. The loss of striataldopamine results in abnormal activity of the basal ganglia, a series ofnuclei which regulate smooth and well co-ordinated movement (Blandini F.et al., Glutamate and Parkinson's Disease. Mol. Neurobiol. 1996, 12,73-94). The neurochemical deficits seen in Parkinson's disease can bereproduced by local injection of the dopaminergic neurotoxin6-hydroxydopamine into brain regions containing either the cell bodiesor axonal fibres of the nigrostriatal neurones.

By unilaterally lesioning the nigrostriatal pathway on only one-side ofthe brain, a behavioural asymmetry in movement inhibition is observed.Although unilaterally-lesioned animals are still mobile and capable ofself maintenance, the remaining dopamine-sensitive neurones on thelesioned side become supersensitive to stimulation. This is demonstratedby the observation that following systemic administration of dopamineagonists, such as apomorphine, animals show a pronounced rotation in adirection contralateral to the side of lesioning. The ability ofcompounds to induce contralateral rotations in 6-OHDA lesioned rats hasproven to be a sensitive model to predict drug efficacy in the treatmentof Parkinson's Disease.

Animals

Male Sprague-Dawley rats, obtained from Charles River, are used for allexperiments. Animals are housed in groups of 5 under 12 hr light/darkcycle (lights on 08:00 hr), in a temperature (20±2° C.) and humidity(55±15%) controlled environment. Animals have free access to food andwater, and are allowed at least 7 days to acclimatize after deliverybefore experimental use.

Drugs

Ascorbic acid, desipramine, 6-OHDA and apomorphine (Sigma-Aldrich,Poole, UK). 6-OHDA is freshly prepared as a solution in 0.2% ascorbateat a concentration of 4 mg/mL prior to surgery. Desipramine is dissolvedin warm saline, and administered in a volume of 1 ml/kg. Apomorphine isdissolved in 0.02% ascorbate and administered in a volume of 2 mL/kg.Test compounds are suspended in 8% Tween and injected in a volume of 2mL/kg.

Surgery

15 minutes prior to surgery, animals are given an intraperitonealinjection of the noradrenergic uptake inhibitor desipramine (25 mg/kg)to prevent damage to non-dopamine neurones. Animals are then placed inan anaesthetic chamber and anaesthetised using a mixture of oxygen andisoflurane. Once unconscious, the animals are transferred to astereotaxic frame, where anaesthesia is maintained through a mask. Thetop of the animal's head is shaved and sterilised using an iodinesolution. Once dry, a 2 cm long incision is made along the midline ofthe scalp and the skin retracted and clipped back to expose the skull. Asmall hole is then drilled through the skill above the injection site.In order to lesion the nigrostriatal pathway, the injection cannula isslowly lowered to position above the right medial forebrain bundle at−3.2 mm anterior posterior, −1.5 mm medial lateral from bregma, and to adepth of 7.2 mm below the duramater. 2 minutes after lowing the cannula,2 μL of 6-OHDA is infused at a rate of 0.5 μL/min over 4 minutes,yielding a final dose of 8 μg. The cannula is then left in place for afurther 5 minutes to facilitate diffusion before being slowly withdrawn.The skin is then sutured shut using Ethicon W501 Mersilk, and the animalremoved from the strereotaxic frame and returned to its homecage. Therats are allowed 2 weeks to recover from surgery before behaviouraltesting.

Apparatus

Rotational behaviour is measured using an eight station rotameter systemprovided by Med Associates, San Diego, USA. Each station is comprised ofa stainless steel bowl (45 cm diameter×15 cm high) enclosed in atransparent Plexiglas cover running around the edge of the bowl, andextending to a height of 29 cm. To assess rotation, rats are placed incloth jacket attached to a spring tether connected to optical rotameterpositioned above the bowl, which assesses movement to the left or righteither as partial (45°) or full (3600) rotations. All eight stations areinterfaced to a computer that tabulated data.

Procedure

To reduce stress during drug testing, rats are initially habituated tothe apparatus for 15 minutes on four consecutive days. On the test day,rats are given an intraperitoneal injection of test compound 30 minutesprior to testing. Immediately prior to testing, animals are given asubcutaneous injection of a subthreshold dose of apomorphine, thenplaced in the harness and the number of rotations recorded for one hour.The total number of full contralatral rotations during the hour testperiod serves as an index of antiparkinsonian drug efficacy.

1. A method of treating a patient suffering from Parkinson's diseasecomprising administering to the patient an effective dose of apharmaceutical composition comprising a compound of formula (I) or apharmaceutically acceptable salt thereof,

at least one additional drug useful in the treatment of Parkinson'sdisease and at least one pharmaceutically acceptable carrier, wherein R₁is selected from the group consisting of H, alkyl, aryl, alkoxy,aryloxy, alkylthio, arylthio, halogen, CN, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆,NR₄CO₂R₇ and NR₄SO₂R₇; R₂ is an aryl attached via an unsaturated ringcarbon of said aryl group; R₃ is selected from the group consisting ofH, alkyl, COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆ and SO₂R₇; R₄, R₅ and R₆ areindependently selected from the group consisting of H, alkyl and aryl,or where R₅ and R₆ are in an NR₅R₆ group, R₅ and R₆ may be linked toform a heterocyclic group, or where R₄, R₅ and R₆ are in a (CONR₄NR₅R₆)group, R₄ and R₅ may be linked to form a heterocyclic group; and R₇ isselected from the group consisting of alkyl and aryl.
 2. The methodaccording to claim 1, wherein the at least one additional drug isevodopa (L-DOPA) or a dopamine agonist.